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Journal of Nuclear Medicine
Journal Prestige (SJR): 2.307
Citation Impact (citeScore): 5
Number of Followers: 24  
 
  Full-text available via subscription Subscription journal
ISSN (Print) 0161-5505
Published by Society of Nuclear Medicine Homepage  [1 journal]
  • This Month in JNM

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      Pages: 8A - 8A
      PubDate: 2021-10-01T07:34:43-07:00
      Issue No: Vol. 62, No. 10 (2021)
       
  • 2021 SNMMI Highlights Lecture: Oncology and Therapy, Part 1

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      Authors: Schoder H.
      Pages: 9N - 15N
      Abstract: From the Newsline Editor: The Highlights Lecture, presented at the closing session of each SNMMI Annual Meeting, was originated and presented for more than 30 years by Henry N. Wagner, Jr., MD. Beginning in 2010, the duties of summarizing selected significant presentations at the meeting were divided annually among 4 distinguished nuclear and molecular medicine subject matter experts. Each year Newsline publishes these lectures and selected images. The 2021 Highlights Lectures were delivered on June 15 as part of the SNMMI Virtual Annual Meeting. In this issue we feature the first part of the lecture by Heiko Schöder, MD, MBA, chief of the Molecular Imaging and Therapy Service at Memorial Sloan Kettering Cancer Center (New York, NY) and a professor of radiology at the Weill Medical College of Cornell University (New York, NY), who spoke on oncology and therapy highlights from the meeting. The second part of the lecture will appear in the November issue of Newsline. Note that in the following presentation summary, numerals in brackets represent abstract numbers as published in The Journal of Nuclear Medicine (2021;62[suppl 1]).
      PubDate: 2021-10-01T07:34:43-07:00
      Issue No: Vol. 62, No. 10 (2021)
       
  • SNMMI Newsline

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      Pages: 11N - 22N
      PubDate: 2021-10-01T07:34:43-07:00
      Issue No: Vol. 62, No. 10 (2021)
       
  • SNMMI and ACGME Equity Matters Initiative

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      Pages: 15N - 15N
      PubDate: 2021-10-01T07:34:43-07:00
      Issue No: Vol. 62, No. 10 (2021)
       
  • Amnon (Amy) Piepsz, MD (1938-2021)

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      Authors: Prigent, A; Blaufox, M. D, Taylor, A, Alazraki, N.
      Pages: 16N - 16N
      PubDate: 2021-10-01T07:34:43-07:00
      Issue No: Vol. 62, No. 10 (2021)
       
  • State of the Society: SNMMI Thrives Despite COVID-19 Challenges

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      Authors: Pappas V.
      Pages: 17N - 17N
      PubDate: 2021-10-01T07:34:43-07:00
      Issue No: Vol. 62, No. 10 (2021)
       
  • Newsbriefs

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      Pages: 18N - 20N
      PubDate: 2021-10-01T07:34:43-07:00
      Issue No: Vol. 62, No. 10 (2021)
       
  • Somatostatin Receptor Imaging and Theranostics: Current Practice and
           Future Prospects

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      Authors: Park, S; Parihar, A. S, Bodei, L, Hope, T. A, Mallak, N, Millo, C, Prasad, K, Wilson, D, Zukotynski, K, Mittra, E.
      Pages: 1323 - 1329
      Abstract: A new era of precision diagnostics and therapy for patients with neuroendocrine neoplasms began with the approval of somatostatin receptor (SSTR) radiopharmaceuticals for PET imaging followed by peptide receptor radionuclide therapy (PRRT). With the transition from SSTR-based -scintigraphy to PET, the higher sensitivity of the latter raised questions regarding the direct application of the planar scintigraphy–based Krenning score for PRRT eligibility. Also, to date, the role of SSTR PET in response assessment and predicting outcome remains under evaluation. In this comprehensive review article, we discuss the current role of SSTR PET in all aspects of neuroendocrine neoplasms, including its relation to conventional imaging, selection of patients for PRRT, and the current understanding of SSTR PET–based response assessment. We also provide a standardized reporting template for SSTR PET with a brief discussion.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.251512
      Issue No: Vol. 62, No. 10 (2021)
       
  • Artificial Intelligence for PET Image Reconstruction

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      Authors: Reader, A. J; Schramm, G.
      Pages: 1330 - 1333
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.121.262303
      Issue No: Vol. 62, No. 10 (2021)
       
  • PET/MRI Improves Management of Children with Cancer

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      Authors: Baratto, L; Hawk, K. E, States, L, Qi, J, Gatidis, S, Kiru, L, Daldrup-Link, H. E.
      Pages: 1334 - 1340
      Abstract: Integrated PET/MRI has shown significant clinical value for staging and restaging of children with cancer by providing functional and anatomic tumor evaluation with a 1-stop imaging test and with up to 80% reduced radiation exposure compared with 18F-FDG PET/CT. This article reviews clinical applications of 18F-FDG PET/MRI that are relevant for pediatric oncology, with particular attention to the value of PET/MRI for patient management. Early adopters from 4 different institutions share their insights about specific advantages of PET/MRI technology for the assessment of young children with cancer. We discuss how whole-body PET/MRI can be of value in the evaluation of certain anatomic regions, such as soft tissues and bone marrow, as well as specific PET/MRI interpretation hallmarks in pediatric patients. We highlight how whole-body PET/MRI can improve the clinical management of children with lymphoma, sarcoma, and neurofibromatosis, by reducing the number of radiologic examinations needed (and consequently the radiation exposure), without losing diagnostic accuracy. We examine how PET/MRI can help in differentiating malignant tumors versus infectious or inflammatory diseases. Future research directions toward the use of PET/MRI for treatment evaluation of patients undergoing immunotherapy and assessment of different theranostic agents are also briefly explored. Lessons learned from applications in children might also be extended to evaluations of adult patients.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.259747
      Issue No: Vol. 62, No. 10 (2021)
       
  • The Latest Advances in Imaging Crosstalk Between the Immune System and
           Fibrosis in Cardiovascular Disease

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      Authors: Heo, G. S; Lou, L, Sultan, D, Liu, Y.
      Pages: 1341 - 1346
      Abstract: Inflammation and fibrosis are hallmarks of tissue repair processes and organ failure progression in cardiovascular diseases. Paradigm-shifting research on diverse immune cell populations within the cardiovascular system have enabled discovery of new biomarkers fostering development of diagnostic and therapeutic agents at the molecular level to better manage cardiovascular diseases. To date, a variety of molecular imaging agents have been developed to visualize the biomarkers expressed on immune cells and fibroblasts within their crosstalk network, which drives the pathogenesis of fibrosis triggered by both innate and adaptive immunity. Herein, key biomarkers upregulated in the immune-fibrosis axis are discussed. The promising molecular imaging agents to reveal this critical pathologic process are summarized.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.255539
      Issue No: Vol. 62, No. 10 (2021)
       
  • Imaging of Small Intestine Neuroendocrine Neoplasms: Is SSTR PET the Holy
           Grail'

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      Authors: Imperiale, A; Meuter, L, Pacak, K, Taieb, D.
      Pages: 1347 - 1348
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.121.262140
      Issue No: Vol. 62, No. 10 (2021)
       
  • Simultaneous Mapping of Vasculature, Hypoxia, and Proliferation Using
           Dynamic Susceptibility Contrast MRI, 18F-FMISO PET, and 18F-FLT PET in
           Relation to Contrast Enhancement in Newly Diagnosed Glioblastoma

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      Authors: Collet, S; Guillamo, J.-S, Berro, D. H, Chakhoyan, A, Constans, J.-M, Lechapt-Zalcman, E, Derlon, J.-M, Hatt, M, Visvikis, D, Guillouet, S, Perrio, C, Bernaudin, M, Valable, S.
      Pages: 1349 - 1356
      Abstract: Conventional MRI plays a key role in the management of patients with high-grade glioma, but multiparametric MRI and PET tracers could provide further information to better characterize tumor metabolism and heterogeneity by identifying regions having a high risk of recurrence. In this study, we focused on proliferation, hypervascularization, and hypoxia, all factors considered indicative of poor prognosis. They were assessed by measuring uptake of 18F-3'-deoxy-3'-18F-fluorothymidine (18F-FLT), relative cerebral blood volume (rCBV) maps, and uptake of 18F-fluoromisonidazole (18F-FMISO), respectively. For each modality, the volumes and high-uptake subvolumes (hot spots) were semiautomatically segmented and compared with the contrast enhancement (CE) volume on T1-weighted gadolinium-enhanced (T1w-Gd) images, commonly used in the management of patients with glioblastoma. Methods: Dynamic susceptibility contrast-enhanced MRI (31 patients), 18F-FLT PET (20 patients), or 18F-FMISO PET (20 patients), for a total of 31 patients, was performed on preoperative glioblastoma patients. Volumes and hot spots were segmented on SUV maps for 18F-FLT PET (using the fuzzy locally adaptive bayesian algorithm) and 18F-FMISO PET (using a mean contralateral image + 3.3 SDs) and on rCBV maps (using a mean contralateral image + 1.96 SDs) for dynamic susceptibility contrast-enhanced MRI and overlaid on T1w-Gd images. For each modality, the percentages of the peripheral volumes and the peripheral hot spots outside the CE volume were calculated. Results: All tumors showed highly proliferated, hypervascularized, and hypoxic regions. The images also showed pronounced heterogeneity of both tracers regarding their uptake and rCBV maps, within each individual patient. Overlaid volumes on T1w-Gd images showed that some proliferative, hypervascularized, and hypoxic regions extended beyond the CE volume but with marked differences between patients. The ranges of peripheral volume outside the CE volume were 1.6%–155.5%, 1.5%–89.5%, and 3.1%–78.0% for 18F-FLT, rCBV, and 18F-FMISO, respectively. All patients had hyperproliferative hot spots outside the CE volume, whereas hypervascularized and hypoxic hot spots were detected mainly within the enhancing region. Conclusion: Spatial analysis of multiparametric maps with segmented volumes and hot spots provides valuable information to optimize the management and treatment of patients with glioblastoma.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.249524
      Issue No: Vol. 62, No. 10 (2021)
       
  • Technologic (R)Evolution Leads to Detection of More Sentinel Nodes in
           Patients with Melanoma in the Head and Neck Region

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      Authors: Berger, D. M. S; van den Berg, N. S, van der Noort, V, van der Hiel, B, Valdes Olmos, R. A, Buckle, T. A, KleinJan, G. H, Brouwer, O. R, Vermeeren, L, Karakullukcu, B, van den Brekel, M. W. M, van de Wiel, B. A, Nieweg, O. E, Balm, A. J. M, van Leeuwen, F. W. B, Klop, W. M. C.
      Pages: 1357 - 1362
      Abstract: Sentinel lymph node (SN) biopsy (SNB) has proven to be a valuable tool for staging melanoma patients. Since its introduction in the early 1990s, this procedure has undergone several technologic refinements, including the introduction of SPECT/CT, as well as radioguidance and fluorescence guidance. The purpose of the current study was to evaluate the effect of this technologic evolution on SNB in the head and neck region. The primary endpoint was the false-negative (FN) rate. Secondary endpoints were number of harvested SNs, overall operation time, operation time per harvested SN, and postoperative complications. Methods: A retrospective database was queried for cutaneous head and neck melanoma patients who underwent SNB at The Netherlands Cancer Institute between 1993 and 2016. The implementation of new detection techniques was divided into 4 groups: 1993–2005, with preoperative lymphoscintigraphy and intraoperative use of both a -ray detection probe and patent blue (n = 30); 2006–2007, with addition of preoperative road maps based on SPECT/CT (n = 15); 2008–2009, with intraoperative use of a portable -camera (n = 40); and 2010–2016, with addition of near-infrared fluorescence guidance (n = 192). Results: In total, 277 patients were included. At least 1 SN was identified in all patients. A tumor-positive SN was found in 59 patients (21.3%): 10 in group 1 (33.3%), 3 in group 2 (20.0%), 6 in group 3 (15.0%), and 40 in group 4 (20.8%). Regional recurrences in patients with tumor-negative SNs resulted in an overall FN rate of 11.9% (group 1, 16.7%; group 2, 0%; group 3, 14.3%; group 4, 11.1%). The number of harvested nodes increased with advancing technologies (P = 0.003), whereas Breslow thickness and operation time per harvested SN decreased (P = 0.003 and P = 0.017, respectively). There was no significant difference in percentage of tumor-positive SNs, overall operation time, and complication rate between the different groups. Conclusion: The use of advanced detection technologies led to a higher number of identified SNs without an increase in overall operation time, possibly indicating an improved surgical efficiency. Operation time per harvested SN decreased; the average FN rate remained 11.9% and was unchanged over 23 y. There was no significant change in postoperative complication rate.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.246819
      Issue No: Vol. 62, No. 10 (2021)
       
  • Diagnostic Value, Oncologic Outcomes, and Safety Profile of Image-Guided
           Surgery Technologies During Robot-Assisted Lymph Node Dissection with
           Sentinel Node Biopsy for Prostate Cancer

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      Authors: Mazzone, E; DellOglio, P, Grivas, N, Wit, E, Donswijk, M, Briganti, A, Leeuwen, F. V, Poel, H. v. d.
      Pages: 1363 - 1371
      Abstract: Despite good sensitivity and a good negative predictive value, the implementation of sentinel node biopsy (SNB) in robot-assisted radical prostatectomy with extended pelvic lymph node dissection (ePLND) for prostate cancer is still controversial. For this reason, we aimed to define the added value of SNB (with different tracer modalities) to ePLND in the identification of nodal metastases. Complication rates and oncologic outcomes were also assessed. Methods: From January 2006 to December 2019, prospectively collected data were retrospectively analyzed from a single-institution database regarding prostate cancer patients treated with robot-assisted radical prostatectomy and ePLND with or without additional use of SNB, either with the hybrid tracer indocyanine green (ICG)–99mTc-nanocolloid or with free ICG. Multivariable logistic and Cox regression models tested the impact of adding SNB (either with the hybrid tracer or with free ICG) on lymph nodal invasion detection, complications, and oncologic outcomes. Results: Overall, 1,680 patients were included in the final analysis: 1,168 (69.5%) in the non-SNB group, 161 (9.6%) in the ICG-SNB group, and 351 (20.9%) in the hybrid-SNB group. The hybrid-SNB group (odds ratio, 1.61; 95%CI, 1.18–2.20; P = 0.002) was an independent predictor of nodal involvement, whereas the ICG-SNB group did not reach independent predictor status when compared with the non-SNB group (odds ratio, 1.35; 95%CI, 0.89–2.03; P = 0.1). SNB techniques were not associated with higher rates of complications. Lastly, use of hybrid SNB was associated with lower rates of biochemical recurrence (0.79; 95%CI, 0.63–0.98) and of clinical recurrence (hazard ratio, 0.76, P = 0.035) than were seen in the non-SNB group. Conclusion: The implementation of hybrid-SNB technique with ICG–99mTc-nanocolloid in prostate cancer improves detection of positive nodes and potentially lowers recurrence rates with subsequent optimization of patient management, without harming patient safety.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.259788
      Issue No: Vol. 62, No. 10 (2021)
       
  • Diagnostic Contribution of Contrast-Enhanced CT as Compared with
           Unenhanced Low-Dose CT in PET/CT Staging and Treatment Response Assessment
           of 18F-FDG-Avid Lymphomas: A Prospective Study

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      Authors: Marchetti, L; Perrucci, L, Pellegrino, F, Baroni, L, Merlo, A, Tilli, M, Rambaldi, I, Maietti, E, Carnevale, A, Bartolomei, M, Giganti, M.
      Pages: 1372 - 1379
      Abstract: The aim of this study was to assess the added diagnostic value of contrast-enhanced CT (CECT) as compared with unenhanced CT (UECT) in PET/CT staging and treatment response assessment of 18F-FDG–avid lymphomas. Methods: 170 PET/UECT scans followed by CECT scans were prospectively performed for staging (n = 85) and for treatment response assessment (n = 85) of 18F-FDG–avid lymphomas, during a single session using an integrated 64-slice PET/CT scanner. CECT and UECT images were evaluated separately by 2 radiologists, whereas PET images were evaluated by 2 nuclear physicians. Nodal and extranodal UECT and CECT findings were classified according to the Lugano criteria and were successively compared with PET/CT results, considered the gold standard. In the analyzed groups, the agreement rate with the disease status determined via PET was calculated separately for UECT and CECT using the McNemar test on paired data. The added value of the contrast medium was shown by the agreement between the PET and CECT results and the lack of agreement between UECT and PET. Results: CECT enabled the identification of additional extranodal lesions (hepatic, muscular, and gastric) in only 3 staging group cases (3.5%), indicating different stages as compared with UECT, whereas there was absolute agreement between CECT and UECT in terms of treatment response assessment. The added diagnostic value of CECT was lower than the established threshold for clinical relevance (15%). The McNemar test indicated no statistical significance in either group. The incidental findings detected by CECT but not UECT were important for clinical management but not sufficient to alter lymphoma treatment strategy. Conclusion: According to our results, it might be possible to exclude CECT examination of 18F-FDG–avid lymphoma from staging and treatment response assessment, with the consequent advantages of reducing radiation exposure and potential contrast-related risks.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.259242
      Issue No: Vol. 62, No. 10 (2021)
       
  • Prognostic Value of Bone Marrow Metabolism on Pretreatment 18F-FDG PET/CT
           in Patients with Metastatic Melanoma Treated with Anti-PD-1 Therapy

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      Authors: Nakamoto, R; Zaba, L. C, Liang, T, Reddy, S. A, Davidzon, G, Aparici, C. M, Nguyen, J, Moradi, F, Iagaru, A, Franc, B. L.
      Pages: 1380 - 1383
      Abstract: Our purpose was to investigate the prognostic value of 18F-FDG PET/CT parameters in melanoma patients before beginning therapy with antibodies to the programmed cell death 1 receptor (anti-PD-1). Methods: Imaging parameters including SUVmax, metabolic tumor volume, and the ratio of bone marrow to liver SUVmean (BLR) were measured from baseline PET/CT in 92 patients before the start of anti-PD-1 therapy. The association with survival and imaging parameters combined with clinical factors was evaluated. Clinical and laboratory data were compared between the high-BLR group (>median) and the low-BLR group (≤median). Results: Multivariate analyses demonstrated that BLR was an independent prognostic factor for progression-free and overall survival (P = 0.017 and P = 0.011, respectively). The high-BLR group had higher white blood cell counts and neutrophil counts and a higher level of C-reactive protein than the low-BLR group (P < 0.05). Conclusion: Patients with a high BLR were associated with poor progression-free and overall survival, potentially explained by evidence of systemic inflammation known to be associated with immunosuppression.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.254482
      Issue No: Vol. 62, No. 10 (2021)
       
  • Exploiting the MUC5AC Antigen for Noninvasive Identification of Pancreatic
           Cancer

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      Authors: Henry, K. E; Shaffer, T. M, Mack, K. N, Ring, J, Ogirala, A, Klein-Scory, S, Eilert-Micus, C, Schmiegel, W, Bracht, T, Sitek, B, Clyne, M, Reid, C. J, Sipos, B, Lewis, J. S, Kalthoff, H, Grimm, J.
      Pages: 1384 - 1390
      Abstract: Pancreatic cancer (PC) remains the fourth leading cause of cancer death; therefore, there is a clinically unmet need for novel therapeutics and diagnostic markers to treat this devastating disease. Physicians often rely on biopsy or CT for diagnosis, but more specific protein biomarkers are highly desired to assess the stage and severity of PC in a noninvasive manner. Serum biomarkers such as carbohydrate antigen 19-9 are of particular interest as they are commonly elevated in PC but have exhibited suboptimal performance in the clinic. MUC5AC has emerged as a useful serum biomarker that is specific for PC versus inflammation. We developed RA96, an anti-MUC5AC antibody, to gauge its utility in PC diagnosis through immunohistochemical analysis and whole-body PET in PC. Methods: In this study, extensive biochemical characterization determined MUC5AC as the antigen for RA96. We then determined the utility of RA96 for MUC5AC immunohistochemistry on clinical PC and preclinical PC. Finally, we radiolabeled RA96 with 89Zr to assess its application as a whole-body PET radiotracer for MUC5AC quantification in PC. Results: Immunohistochemical staining with RA96 distinguished chronic pancreatitis, pancreatic intraepithelial neoplasia, and varying grades of pancreatic ductal adenocarcinoma in clinical samples. 89Zr-desferrioxamine-RA96 was able to detect MUC5AC with high specificity in mice bearing capan-2 xenografts. Conclusion: Our study demonstrated that RA96 can differentiate between inflammation and PC, improving the fidelity of PC diagnosis. Our immuno-PET tracer 89Zr-desferrioxamine-RA96 shows specific detection of MUC5AC-positive tumors in vivo, highlighting the utility of MUC5AC targeting for diagnosis of PC.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.256776
      Issue No: Vol. 62, No. 10 (2021)
       
  • First-in-Humans Application of 161Tb: A Feasibility Study Using
           161Tb-DOTATOC

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      Authors: Baum, R. P; Singh, A, Kulkarni, H. R, Bernhardt, P, Ryden, T, Schuchardt, C, Gracheva, N, Grundler, P. V, Koster, U, Muller, D, Prohl, M, Zeevaart, J. R, Schibli, R, van der Meulen, N. P, Muller, C.
      Pages: 1391 - 1397
      Abstract: 161Tb has decay properties similar to those of 177Lu but, additionally, emits a substantial number of conversion and Auger electrons. The aim of this study was to apply 161Tb in a clinical setting and to investigate the feasibility of visualizing the physiologic and tumor biodistributions of 161Tb-DOTATOC. Methods: 161Tb was shipped from Paul Scherrer Institute, Villigen-PSI, Switzerland, to Zentralklinik Bad Berka, Bad Berka, Germany, where it was used for the radiolabeling of DOTATOC. In 2 separate studies, 596 and 1,300 MBq of 161Tb-DOTATOC were administered to a 35-y-old male patient with a metastatic, well-differentiated, nonfunctional malignant paraganglioma and a 70-y-old male patient with a metastatic, functional neuroendocrine neoplasm of the pancreatic tail, respectively. Whole-body planar -scintigraphy images were acquired over a period of several days for dosimetry calculations. SPECT/CT images were reconstructed using a recently established protocol and visually analyzed. Patients were observed for adverse events after the application of 161Tb-DOTATOC. Results: The radiolabeling of DOTATOC with 161Tb was readily achieved with a high radiochemical purity suitable for patient application. Planar images and dosimetry provided the expected time-dependent biodistribution of 161Tb-DOTATOC in the liver, kidneys, spleen, and urinary bladder. SPECT/CT images were of high quality and visualized even small metastases in bones and liver. The application of 161Tb-DOTATOC was well tolerated, and no related adverse events were reported. Conclusion: This study demonstrated the feasibility of imaging even small metastases after the injection of relatively low activities of 161Tb-DOTATOC using -scintigraphy and SPECT/CT. On the basis of this essential first step in translating 161Tb to clinics, further efforts will be directed toward the application of 161Tb for therapeutic purposes.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.258376
      Issue No: Vol. 62, No. 10 (2021)
       
  • A Prospective, Randomized, Double-Blind Study to Evaluate the Safety,
           Biodistribution, and Dosimetry of 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 in
           Patients with Well-Differentiated Neuroendocrine Tumors

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      Authors: Zhu, W; Cheng, Y, Jia, R, Zhao, H, Bai, C, Xu, J, Yao, S, Huo, L.
      Pages: 1398 - 1405
      Abstract: 68Ga-NODAGA-LM3 (where LM3 is p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH2) and 68Ga-DOTA-LM3 are somatostatin receptor subtype 2 (SSTR2)–specific antagonists used for PET/CT imaging. The purpose of this study was to evaluate the safety, biodistribution, and dosimetry of 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 in patients with well-differentiated neuroendocrine tumors. Methods: Patients were equally randomized into 2 arms, with arm A receiving 68Ga-NODAGA-LM3 and arm B receiving 68Ga-DOTA-LM3. Serial PET scans were acquired at 5, 15, 30, 45, 60, and 120 min after 68Ga-NODAGA-LM3 (200 MBq ± 11 MBq/40 μg of total peptide mass) or 68Ga-DOTA-LM3 (172 MBq ± 21 MBq/40 μg of total peptide mass) injection. The biodistribution in normal organs, tumor uptake, and safety were assessed. Radiation dosimetry was calculated using OLINDA/EXM (version 1.0). Results: Sixteen patients, 8 in each arm, were recruited in the study. Both tracers were well tolerated in most patients. Two patients in arm B had nausea (grade 2), and one of them had vomiting (grade 1). The PET images of the other 14 patients were further analyzed. Significantly lower organ uptake was observed in the pituitary, parotids, liver, spleen, pancreas, adrenal, stomach, small intestine, and kidneys with 68Ga-DOTA-LM3 than with 68Ga-NODAGA-LM3. In total, 38 lesions were analyzed, including 18 with 68Ga-NODAGA-LM3 and 20 with 68Ga-DOTA-LM3. Both tracers showed good tumor uptake and retention. With 68Ga-NODAGA-LM3, the tracer accumulation in tumor lesions increased by 138%, from an average SUVmax of 31.3 ± 19.7 at 5 min to 74.6 ± 56.3 at 2 h. With 68Ga-DOTA-LM3, the tumor uptake rapidly reached a high level at 5 min after injection, with an average SUVmax of 36.6 ± 23.6, and continued to increase to 45.3 ± 29.3 until 30 min after injection. The urinary bladder wall was the organ receiving the highest absorbed dose in both arms. The mean effective dose was 0.026 ± 0.003 mSv/MBq for 68Ga-NODAGA-LM3 and 0.025 ± 0.002 mSv/MBq for 68Ga-DOTA-LM3. Conclusion: Both 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 show favorable biodistribution, high tumor uptake, and good tumor retention, resulting in high image contrast. The dosimetric data are comparable to those for other 68Ga-labeled SSTR2 antagonists. Further studies are required to look into the potential antagonistic effects of 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.253096
      Issue No: Vol. 62, No. 10 (2021)
       
  • Quantitative 68Ga-DOTATATE PET/CT Parameters for the Prediction of Therapy
           Response in Patients with Progressive Metastatic Neuroendocrine Tumors
           Treated with 177Lu-DOTATATE

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      Authors: Ortega, C; Wong, R. K. S, Schaefferkoetter, J, Veit-Haibach, P, Myrehaug, S, Juergens, R, Laidley, D, Anconina, R, Liu, A, Metser, U.
      Pages: 1406 - 1414
      Abstract: The aim of this study was to determine whether quantitative PET parameters on baseline 68Ga-DOTATATE PET/CT and interim PET (iPET) performed before the second cycle of therapy are predictive of the therapy response and progression-free survival (PFS). Methods: Ninety-one patients with well-differentiated neuroendocrine tumors (mean Ki-67 index, 8.3%) underwent 68Ga-DOTATATE PET/CT to determine suitability for peptide receptor radionuclide therapy as part of a prospective multicenter study. The mean follow-up was 12.2 mo. Of the 91 patients, 36 had iPET. The tumor metrics evaluated were marker lesion–based measures (mean SUVmax and ratio of the mean lesion SUVmax to the SUVmax in the liver or the SUVmax in the spleen), segmented 68Ga-DOTATATE tumor volumes (DTTVs), SUVmax and SUVmean obtained with the liver and spleen as thresholds, and heterogeneity parameters (coefficient of variation, kurtosis, and skewness). The Wilcoxon rank sum test was used for the association between continuous variables and the therapy response, as determined by the clinical response. Univariable and multivariable Cox proportional hazards models were used for the association with PFS. Results: There were 71 responders and 20 nonresponders. When marker lesions were used, higher mean SUVmax and ratio of the mean lesion SUVmax to the SUVmax in the liver were predictors of the therapy response (P = 0.018 and 0.024, respectively). For DTTV parameters, higher SUVmax and SUVmean obtained with the liver as a threshold and lower kurtosis were predictors of a favorable response (P = 0.025, 0.0055, and 0.031, respectively). The latter also correlated with a longer PFS. The iPET DTTV SUVmean obtained with the liver as a threshold and the ratio of mean SUVmax obtained from target lesions at iPET to baseline PET correlated with the therapy response (P = 0.024 and 0.048, respectively) but not PFS. From the multivariable analysis with adjustment for age, primary site, and Ki-67 index, the mean SUVmax (P = 0.019), ratio of the mean lesion SUVmax to the SUVmax in the liver (P = 0.018), ratio of the mean lesion SUVmax to the SUVmax in the spleen (P = 0.041), DTTV SUVmean obtained with the liver (P = 0.0052), and skewness (P = 0.048) remained significant predictors of PFS. Conclusion: The degree of somatostatin receptor expression and tumor heterogeneity, as represented by several metrics in our analysis, were predictive of the therapy response or PFS. Changes in these parameters after the first cycle of peptide receptor radionuclide therapy did not correlate with clinical outcomes.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.256727
      Issue No: Vol. 62, No. 10 (2021)
       
  • Improved Primary Staging of Marginal-Zone Lymphoma by Addition of
           CXCR4-Directed PET/CT

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      Authors: Duell, J; Krummenast, F, Schirbel, A, Klassen, P, Samnick, S, Rauert-Wunderlich, H, Rasche, L, Buck, A. K, Wester, H.-J, Rosenwald, A, Einsele, H, Topp, M. S, Lapa, C, Kircher, M.
      Pages: 1415 - 1421
      Abstract: PET/CT with 18F-FDG is an integral component in the primary staging of most lymphomas. However, its utility is limited in marginal-zone lymphoma (MZL) because of inconsistent 18F-FDG avidity. One diagnostic alternative could be the targeting of C-X-C motif chemokine receptor 4 (CXCR4), shown to be expressed by MZL cells. This study investigated the value of adding CXCR4-directed 68Ga-pentixafor PET/CT to conventional staging. Methods: Twenty-two newly diagnosed MZL patients were staged conventionally and with CXCR4 PET/CT. Lesions identified exclusively by CXCR4 PET/CT were biopsied as the standard of reference and compared with imaging results. The impact of CXCR4-directed imaging on staging results and treatment protocol was assessed. Results: CXCR4 PET/CT correctly identified all patients with viable MZL and was superior to conventional staging (P < 0.001). CXCR4-directed imaging results were validated by confirmation of MZL in 16 of 18 PET-guided biopsy samples. Inclusion of CXCR4 PET/CT in primary staging significantly impacted staging results in almost half of patients and treatment protocols in a third (upstaging, n = 7; downstaging, n = 3; treatment change, n = 8; P < 0.03). Conclusion: CXCR4 PET/CT is a suitable tool in primary staging of MZL and holds the potential to improve existing diagnostic algorithms.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.257279
      Issue No: Vol. 62, No. 10 (2021)
       
  • Matched-Pair Comparison of 18F-DCFPyL PET/CT and 18F-PSMA-1007 PET/CT in
           240 Prostate Cancer Patients: Interreader Agreement and Lesion Detection
           Rate of Suspected Lesions

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      Authors: Wondergem, M; van der Zant, F. M, Broos, W. A. M, Knol, R. J. J.
      Pages: 1422 - 1429
      Abstract: Over 20 different prostate-specific membrane antigen (PSMA)–targeting radiopharmaceuticals for both imaging and therapy have been synthesized. Although variability in biodistribution and affinity for binding to the PSMA receptor is known to exist between different PSMA-targeting radiopharmaceuticals, little is known about the clinical implications of this variability. Therefore, this study analyzed differences in interreader agreement and detection rate between 2 regularly used 18F-labeled PSMA receptor–targeting radiopharmaceuticals: 18F-DCFPyL and 18F-PSMA-1007. Methods: One hundred twenty consecutive patients scanned with 18F-PSMA-1007 were match-paired with 120 patients scanned with 18F-DCFPyL. All 240 PET/CT scans were reviewed by 2 readers and scored according to the criteria of the PSMA Reporting and Data System. Interreader agreement and the detection rate for suspected lesions were scored for different anatomic locations such as the prostate, prostatic fossa, lymph nodes, and bone. Results: Great equality was found between 18F-DCFPyL and 18F-PSMA-1007; however, some clinically relevant and statistically significant differences were observed. 18F-PSMA-1007 detected suspected prostatic or prostatic fossa lesions in a higher proportion of patients and especially in the subcohort scanned for biochemical recurrence. 18F-DCFPyL and 18F-PSMA-1007 showed an equal ability to detect suspected lymph nodes, although interreader agreement for 18F-DCFPyL was higher. 18F-DCFPyL showed fewer equivocal skeletal lesions and higher interreader agreement on skeletal lesions. Most of the equivocal lesions found with 18F-PSMA-1007 at least were determined to be of nonmetastatic origin. Conclusion: Clinically relevant differences, which may account for diagnostic dilemmas, were observed between 18F-DCFPyL and 18F-PSMA-1007. Those findings encourage further studies, as they may have consequences for selection of the proper PSMA-targeting radiopharmaceutical.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.258574
      Issue No: Vol. 62, No. 10 (2021)
       
  • Prospective, Single-Arm Trial Evaluating Changes in Uptake Patterns on
           Prostate-Specific Membrane Antigen-Targeted 18F-DCFPyL PET/CT in Patients
           with Castration-Resistant Prostate Cancer Starting Abiraterone or
           Enzalutamide

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      Authors: Zukotynski, K. A; Emmenegger, U, Hotte, S, Kapoor, A, Fu, W, Blackford, A. L, Valliant, J, Benard, F, Kim, C. K, Markowski, M. C, Eisenberger, M. A, Antonarakis, E. S, Pienta, K. J, Gorin, M. A, Lubanovic, M, Kim, J, Pomper, M. G, Cho, S. Y, Rowe, S. P.
      Pages: 1430 - 1437
      Abstract: PET with small molecules targeting prostate-specific membrane antigen (PSMA) is being adopted as a clinical standard for prostate cancer imaging. In this study, we evaluated changes in uptake on PSMA-targeted PET in men starting abiraterone or enzalutamide. Methods: This prospective, single-arm, 2-center, exploratory clinical trial enrolled men with metastatic castration-resistant prostate cancer initiating abiraterone or enzalutamide. Each patient was imaged with 18F-DCFPyL at baseline and within 2–4 mo after starting therapy. Patients were followed for up to 48 mo from enrollment. A central review evaluated baseline and follow-up PET scans, recording change in SUVmax at all disease sites and classifying the pattern of change. Two parameters were derived: the -percent SUVmax (DPSM) of all lesions and the -absolute SUVmax (DASM) of all lesions. Kaplan–Meier curves were used to estimate time to therapy change (TTTC) and overall survival (OS). Results: Sixteen evaluable patients were accrued to the study. Median TTTC was 9.6 mo (95% CI, 6.9–14.2), and median OS was 28.6 mo (95% CI, 18.3–not available [NA]). Patients with a mixed-but-predominantly-increased pattern of radiotracer uptake had a shorter TTTC and OS. Men with a low DPSM had a median TTTC of 12.2 mo (95% CI, 11.3–NA) and a median OS of 37.2 mo (95% CI, 28.9–NA), whereas those with a high DPSM had a median TTTC of 6.5 mo (95% CI, 4.6–NA, P = 0.0001) and a median OS of 17.8 mo (95% CI, 13.9–NA, P = 0.02). Men with a low DASM had a median TTTC of 12.2 mo (95% CI, 11.3–NA) and a median OS of NA (95% CI, 37.2 mo–NA), whereas those with a high DASM had a median TTTC of 6.9 mo (95% CI, 6.1–NA, P = 0.003) and a median OS of 17.8 mo (95% CI, 13.9–NA, P = 0.002). Conclusion: Findings on PSMA-targeted PET 2–4 mo after initiation of abiraterone or enzalutamide are associated with TTTC and OS. Development of new lesions or increasing intensity of radiotracer uptake at sites of baseline disease are poor prognostic findings suggesting shorter TTTC and OS.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.259069
      Issue No: Vol. 62, No. 10 (2021)
       
  • RESIST-PC: U.S. Academic Foray into PSMA Theranostic Trials

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      Authors: Iravani, A; Hope, T. A.
      Pages: 1438 - 1439
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.121.262602
      Issue No: Vol. 62, No. 10 (2021)
       
  • Prospective phase 2 trial of PSMA-targeted molecular RadiothErapy with
           177Lu-PSMA-617 for metastatic castration-reSISTant Prostate Cancer
           (RESIST-PC): efficacy results of the UCLA cohort

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      Authors: Calais, J; Gafita, A, Eiber, M, Armstrong, W. R, Gartmann, J, Thin, P, Nguyen, K, Lok, V, Gosa, L, Grogan, T, Esfandiari, R, Allen-Auerbach, M, Quon, A, Bahri, S, Gupta, P, Gardner, L, Ranganathan, D, Slavik, R, Dahlbom, M, Herrmann, K, Delpassand, E, Fendler, W. P, Czernin, J.
      Pages: 1440 - 1446
      Abstract: The objective of this study was to determine prospectively the efficacy profile of 2 activity regimens of 177Lu-PSMA therapy in patients with progressive metastatic castrate-resistant prostate cancer (mCRPC): 6.0 vs. 7.4 GBq. Methods: RESIST-PC (NCT03042312) was a prospective multicenter phase 2 trial. Patients with progressive mCRPC after ≥ 1 novel androgen-axis drug, either chemotherapy naïve or postchemotherapy, with sufficient bone marrow reserve, normal kidney function, and sufficient PSMA expression by PSMA PET were eligible. Patients were randomized (1:1) into 2 activity groups (6.0 or 7.4 GBq) and received up to 4 cycles every 8 wk. The primary endpoint was the efficacy of 177Lu-PSMA measured by the prostate-specific antigen (PSA) response rate (RR) after 2 cycles (≥50% decline from baseline). Secondary endpoints included the PSA RR (≥50% decline) at any time (best response), and overall survival (OS). Results: The study was closed at enrollment of 71/200 planned patients because of sponsorship transfer. We report here the efficacy of the University of California Los Angeles cohort results only (n = 43). The PSA RRs after 2 cycles and at any time were 11/40 (28%, 95% CI 15–44), 6/13 (46%, 95% CI 19–75), and 5/27 (19%, 95% CI 6–38), and 16/43 (37%, 95% CI 23–53), 7/14 (50%, 95% CI 23–77), and 9/29 (31%, 95% CI 15–51) in the whole cohort, the 6.0-GBq group, and the 7.4-GBq group, respectively (P = 0.12 and P = 0.31). The median OS was 14.0 mo (95% CI 10.1–17.9), 15.8 (95% CI 11.8–19.4), and 13.5 (95% CI 10.0–17.0) in the whole cohort, the 6.0-GBq group, and the 7.4 GBq group, respectively (P = 0.87). OS was longer in patients who experienced a PSA decline ≥ 50% at any time than in those who did not: median, 20.8 versus 10.8 mo (P = 0.005). Conclusion: In this prospective phase 2 trial of 177Lu-PSMA for mCRPC, the median OS was 14 mo. Despite the heterogeneous study population and the premature study termination, the efficacy profile of 177Lu-PSMA appeared to be favorable and comparable with both activity regimens (6.0 vs. 7.4 GBq). Results justify confirmation with real-world data matched-pair analysis and further clinical trials to refine and optimize the 177Lu-PSMA therapy administration scheme to improve tumor radiation dose delivery and efficacy.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.121.261982
      Issue No: Vol. 62, No. 10 (2021)
       
  • Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617:
           Results from the Prospective Multicenter Phase 2 Trial RESIST-PC
           (NCT03042312)

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      Authors: Calais, J; Czernin, J, Thin, P, Gartmann, J, Nguyen, K, Armstrong, W. R, Allen-Auerbach, M, Quon, A, Bahri, S, Gupta, P, Gardner, L, Dahlbom, M, He, B, Esfandiari, R, Ranganathan, D, Herrmann, K, Eiber, M, Fendler, W. P, Delpassand, E.
      Pages: 1447 - 1456
      Abstract: The purpose of this analysis was to report the safety evaluation of 177Lu-PSMA-617 derived from the cohort of 64 patients exposed to 177Lu-PSMA-617 in the RESIST-PC trial NCT03042312. Methods: RESIST-PC was a prospective multicenter phase 2 trial. Patients with progressive metastatic castration-resistant prostate cancer after ≥ 1 novel androgen-axis drug, either chemotherapy naïve or postchemotherapy, with sufficient bone marrow reserve, normal kidney function, sufficient PSMA expression by PSMA PET, and no PSMA-negative soft-tissue lesions were eligible. Patients were randomized (1:1) into 2 activity groups (6.0 or 7.4 GBq per cycle) and received up to 4 cycles every 8 wk. The primary safety endpoint was assessed by collecting and grading adverse events using the Common Terminology Criteria for Adverse Events. Patients were followed until disease progression, death, serious or intolerable adverse events, study termination by sponsor, patient withdrawal, lost to follow-up, or 24 mo after the first cycle. Results: The study was closed at enrollment of 71 of 200 planned patients because of sponsorship transfer. A total of 64 (90.1%) patients received at least 1 cycle of 177Lu-PSMA-617: 28 (36%) in arm 1 (6.0 GBq) and 41 (64%) in arm 2 (7.4 GBq). There were 10 (43.5%), 19 (46.5%), and 29 (45.3%) patients who completed 4 cycles of 177Lu-PSMA-617 in the 6.0-GBq arm, 7.4-GBq arm, and overall, respectively. The most common treatment-emergent adverse events (TEAEs) of any grade in the 6.0-GBq arm, the 7.4-GBq arm and overall, were dry mouth (47.8%; 63.4%; 57.8%, respectively), fatigue (56.5%; 51.2%; 53.1%, respectively), nausea (52.2%; 43.9%; 46.9%, respectively), and diarrhea (13.0%; 31.7%; 25.0%, respectively). Frequencies of all other TEAEs were comparable among the 2 groups (within 10% difference). Serious possibly drug-related TEAEs were reported for 5 (7.8%) patients overall (none were considered as probably or definitely related to treatment): 1 subdural hematoma grade 4, 1 anemia grade 3, 1 thrombocytopenia grade 4, 1 gastrointestinal hemorrhage grade 3, and 1 acute kidney injury grade 3. There were no clinically significant changes in vital signs in electrocardiograms in the 2 treatment groups. No trend to creatinine increase or increasing frequency of shifts from normal to abnormal over time for any hematologic parameter was noted. Conclusion: 177Lu-PSMA-617 was safe and well-tolerated at 6.0 and 7.4 GBq per cycle given at 8-wk intervals with side effects easily managed with standard medical support. With established safety, further clinical trials applying individualized dosimetry and testing different 177Lu-PSMA-617 administration schemes (activity levels, time intervals) are needed to optimize tumor dose delivery and treatment efficacy.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.121.262543
      Issue No: Vol. 62, No. 10 (2021)
       
  • Head-to-Head Comparison of 68Ga-NOTA (68Ga-NGUL) and 68Ga-PSMA-11 in
           Patients with Metastatic Prostate Cancer: A Prospective Study

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      Authors: Suh, M; Im, H.-J, Ryoo, H. G, Kang, K. W, Jeong, J. M, Prakash, S, Ballal, S, Yadav, M. P, Bal, C, Jeong, C. W, Kwak, C, Cheon, G. J.
      Pages: 1457 - 1460
      Abstract: 68Ga-NOTA Glu-Urea-Lys (NGUL) is a novel prostate-specific membrane antigen (PSMA)–targeting tracer used for PET/CT imaging. This study aimed to compare performance in the detection of primary and metastatic lesions and to compare biodistribution between 68Ga-NGUL and 68Ga-PSMA-11 in the same patients with prostate cancer. Methods: Eleven patients with metastatic prostate cancer were prospectively recruited. The quantitative tracer uptake was determined in normal organs and in primary and metastatic lesions. Results: 68Ga-NGUL showed significantly lower normal-organ uptake and rapid urinary clearance. The number and sites of detected PSMA-positive primary and metastatic lesions were identical, and no significant quantitative uptake difference was observed. 68Ga-NGUL showed a relatively lower tumor-to-background ratio than 68Ga-PSMA-11. Conclusion: In a head-to-head comparison with 68Ga-PSMA-11, 68Ga-NGUL showed lower uptake in normal organs and similar performance in detecting PSMA-avid primary and metastatic lesions. 68Ga-NGUL could be a valuable option for PSMA imaging.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.258434
      Issue No: Vol. 62, No. 10 (2021)
       
  • Rational Linker Design to Accelerate Excretion and Reduce Background
           Uptake of Peptidomimetic PSMA-Targeting Hybrid Molecules

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      Authors: Eder, A.-C; Schafer, M, Schmidt, J, Bauder-Wust, U, Roscher, M, Leotta, K, Haberkorn, U, Kopka, K, Eder, M.
      Pages: 1461 - 1467
      Abstract: The evolution of peptidomimetic hybrid molecules for preoperative imaging and guided surgery targeting the prostate-specific membrane antigen (PSMA) significantly progressed over the past few years, and some approaches are currently being evaluated for further clinical translation. However, accumulation in nonmalignant tissue such as kidney, bladder, spleen, or liver might limit tumor-to-background contrast for precise lesion delineation, particularly in a surgical setting. To overcome these limitations, a rational linker design aims at the development of a second generation of PSMA-11–based hybrid molecules with an enhanced pharmacokinetic profile and improved imaging contrast. Methods: A selection of rationally designed linkers was introduced to the PSMA-targeting hybrid molecule Glu-urea-Lys-HBED-CC-IRDye800CW, resulting in a second-generation peptidomimetic hybrid molecule library. The biologic properties were investigated in cell-based assays. In a preclinical proof-of-concept study with the radionuclide 68Ga, the impact of the modifications was evaluated by determination of specific tumor uptake, pharmacokinetics, and fluorescence imaging in tumor-bearing mice. Results: The modified hybrid molecules carrying various selected linkers revealed high PSMA-specific binding affinity and effective internalization. The highest tumor-to-background contrast of all modifications investigated was identified for the introduction of a histidine- (H) and glutamic acid (E)–containing linker ((HE)3-linker) between the PSMA-binding motif and the chelator. In comparison to the parental core structure, uptake in nonmalignant tissue was significantly reduced to a minimum, as exemplified by an 11-fold reduced spleen uptake from 38.12 ± 14.62 percentage injected dose (%ID)/g to 3.47 ± 1.39 %ID/g (1 h after injection). The specific tumor uptake of this compound (7.59 ± 0.95 %ID/g, 1 h after injection) was detected to be significantly higher than that of the parental tracer PSMA-11. These findings confirmed by PET and fluorescence imaging are accompanied by an enhanced pharmacokinetic profile with accelerated background clearance at early time points after injection. Conclusion: The novel generation of PSMA-targeting hybrid molecules reveals fast elimination, reduced background organ enrichment, and high PSMA-specific tumor uptake meeting the key demands for potent tracers in nuclear medicine and fluorescence-guided surgery. The approach’s efficacy in improving the pharmacokinetic profile highlights the strengths of rational linker design as a powerful tool in strategic hybrid-molecule development.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.248443
      Issue No: Vol. 62, No. 10 (2021)
       
  • Utility of 211At-Trastuzumab for the Treatment of Metastatic Gastric
           Cancer in the Liver: Evaluation of a Preclinical
           {alpha}-Radioimmunotherapy Approach in a Clinically Relevant Mouse Model

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      Authors: Li, H. K; Morokoshi, Y, Kodaira, S, Kusumoto, T, Minegishi, K, Kanda, H, Nagatsu, K, Hasegawa, S.
      Pages: 1468 - 1474
      Abstract: A liver metastasis from a primary gastric cancer (LMGC) is relatively common and results in an extremely poor prognosis due to a lack of effective therapeutics. We here demonstrate in a clinically relevant mouse model that an α-particle radioimmunotherapy approach with 211At-labeled trastuzumab has efficacy against LMGCs that are positive for human epidermal growth factor receptor 2 (HER2). Methods: 211At was produced in a cyclotron via a 209Bi (α,2n) 211At reaction. 211At-trastuzumab was subsequently generated using a single-step labeling method. NCI-N87 cells (HER2-positive human gastric cancer cells) carrying a luciferase gene were intrasplenically transplanted into severe combined immunodeficiency mice to generate an HER2-positive LMGC model. A biodistribution study was then conducted through the intravenous injection of 211At-trastuzumab (1 MBq) into these LMGC xenograft mice. In parallel with this experimental therapy, phosphate-buffered saline, intact trastuzumab, or 211At-nonspecific human IgG (1 MBq) was injected into control groups. The therapeutic efficacy was evaluated by monitoring tumor changes by chemiluminescence imaging. Body weights, white blood cell counts, and serum markers of tissue damage were monitored at regular intervals. Microdosimetry using a CR-39 plastic detector was also performed. Results: The biodistribution analysis revealed an increased uptake of 211At-trastuzumab in the metastasized tumors that reached approximately 12% of the injected dose per gram of tissue (%ID/g) at 24 h. In contrast, its uptake to the surrounding liver was about 4 %ID/g. The LMGCs in the mouse model reduced dramatically at 1 wk after the single systemic injection of 211At-trastuzumab. No recurrences were observed in 6 of 8 mice treated with this single injection, and their survival time was significantly prolonged compared with the control groups, including the animals treated with 211At-nonspecific antibodies. No severe toxicities or abnormalities in terms of body weight, white blood cell number, liver function, or kidney parameters were observed in the 211At-trastuzumab group. Microdosimetric studies further revealed that 211At-trastuzumab had been delivered at an 11.5-fold higher dose to the LMGC lesions than to the normal liver. Conclusion: α-radioimmunotherapy with 211At-trastuzumab has considerable potential as an effective and safe therapeutic option for LMGC.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.249300
      Issue No: Vol. 62, No. 10 (2021)
       
  • Identification of a PET Radiotracer for Imaging of the Folate
           Receptor-{alpha}: A Potential Tool to Select Patients for Targeted Tumor
           Therapy

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      Authors: Guzik, P; Fang, H.-Y, Deberle, L. M, Benešova, M, Cohrs, S, Boss, S. D, Ametamey, S. M, Schibli, R, Muller, C.
      Pages: 1475 - 1481
      Abstract: The aim of this study was to identify a folate receptor-α (FRα)–selective PET agent potentially suitable for the selection of patients who might profit from FRα-targeted therapies. The 6R and 6S isomers of 18F-aza-5-methyltetrahydrofolate (MTHF) were assessed regarding their binding to FRα and FRβ, expressed on cancer and inflammatory cells, respectively, and compared with 18F-AzaFol, the folic acid–based analog. Methods: FR selectivity was investigated using FRα-transfected (RT16) and FRβ-transfected (D4) CHO cells. The cell uptake of 18F-folate tracers was investigated, and receptor-binding affinities were determined with the nonradioactive analogs. In vitro autoradiography of the 18F-folate tracers was performed using RT16 and D4 tissue sections. Biodistribution studies and PET/CT imaging of the radiotracers were performed on mice bearing RT16 and D4 xenografts. Results: The uptake of 18F-6R-aza-5-MTHF was high when using RT16 cells (62% ± 10% of added activity) but much lower when using D4 cells (5% ± 2%). The FRα selectivity of 18F-6R-aza-5-MTHF was further demonstrated by its approximately 43-fold higher binding affinity to FRα (half-maximal inhibitory concentration [IC50], 1.8 ± 0.1 nM) than to FRβ (IC50, 77 ± 27 nM). The uptake of 18F-6S-aza-5-MTHF and 18F-AzaFol was equal in both cell lines (52%–70%), with similar affinities to FRα (IC50, 2.1 ± 0.4 nM and 0.6 ± 0.3 nM, respectively) and FRβ (0.8 ± 0.2 nM and 0.3 ± 0.1 nM, respectively). The autoradiography signal obtained with 18F-6R-aza-5-MTHF was 11-fold more intense for RT16 than for D4 tissue sections. Biodistribution data showed high uptake of 18F-6R-aza-5-MTHF in RT16 xenografts (81% ± 20% injected activity per gram [IA]/g 1 h after injection) but significantly lower accumulation in D4 xenografts (7.3% ± 2.1% IA/g 1 h after injection), which was also visualized using PET. The uptake of 18F-6S-aza-5-MTHF and 18F-AzaFol was similar in RT16 (53% ± 10% IA/g and 45% ± 2% IA/g, respectively) and D4 xenografts (77% ± 10% IA/g and 52% ± 7% IA/g, respectively). Conclusion: This study demonstrated FRα selectivity for 18F-6R-aza-5-MTHF but not for 18F-6S-aza-5-MTHF or 18F-AzaFol. This characteristic, together with its favorable tissue distribution, makes 18F-6R-aza-5-MTHF attractive for clinical translation to enable detection of FRα-positive cancer while preventing undesired accumulation in FRβ-expressing inflammatory cells.
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.120.255760
      Issue No: Vol. 62, No. 10 (2021)
       
  • PSMA-Targeted Therapeutics: A Tale About Law and Economics

    • Free pre-print version: Loading...

      Authors: Notni J.
      Pages: 1482 - 1482
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.121.262308
      Issue No: Vol. 62, No. 10 (2021)
       
  • 18F-FDG-Avid Axillary Lymph Nodes After COVID-19 Vaccination

    • Free pre-print version: Loading...

      Authors: Johnson, B. J; Van Abel, K. M, Ma, D. J, Johnson, D. R.
      Pages: 1483 - 1484
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.121.262108
      Issue No: Vol. 62, No. 10 (2021)
       
  • Reply: PSMA-Targeted Therapeutics: A Tale About Law and Economics

    • Free pre-print version: Loading...

      Authors: Czernin J.
      Pages: 1483 - 1483
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.121.262566
      Issue No: Vol. 62, No. 10 (2021)
       
  • Specific and Nonspecific Uptake in Quantitative 89Zr-Immuno-PET

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      Authors: Laffon, E; Marthan, R.
      Pages: 1484 - 1485
      PubDate: 2021-10-01T07:34:43-07:00
      DOI: 10.2967/jnumed.121.262065
      Issue No: Vol. 62, No. 10 (2021)
       
 
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