Journal of Nuclear Medicine

Our medical research library holds 6 studies published in Journal of Nuclear Medicine (1985–2021). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 6 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Society of Nuclear Medicine
• Published: 1960 to the present, United States
• Language: English
• ISSN: 0161-5505 (print), 1535-5667 (electronic)
• Its record in the NLM Catalog

2020s

• Volumetric PET Response Assessment Outperforms Conventional Criteria in Patients Receiving High-Dose Pembrolizumab for Malignant Mesothelioma. J. Ferdinandus, F. Barbato, M. Chodyla, et al. 2021;62(2):191-194. PubMed · Publisher

  Abstract

  Fixed-dose pembrolizumab (200 mg absolute, day 1, every 3 wk) for the treatment of malignant pleural mesothelioma did not result in survival benefit in the phase 3 PROMISE-meso trial compared with second-line chemotherapy. Because of lack of validated imaging response criteria, responder subgroups with potential survival benefit have not yet been identified. Here, we administered high-dose pembrolizumab (10 mg/kg, day 1, every 2 wk) considering the KEYNOTE-028 trial and assessed the prognostic value of PET metabolic response in patients with chemotherapy-resistant malignant mesothelioma of the pleura or peritoneum. Methods: Data from 27 patients with baseline and follow-up 18F-FDG PET/CT imaging were retrospectively analyzed. RECIST, version 1.1; modified RECIST; and PERCIST using both tumor lesion metabolic activity in a 1 cm3 spheric region of interest of up to 5 target lesions (PERCISTSULpeak) and metabolic tumor volume PERCIST (PERCISTMTV) were applied separately to categorize responders in CT and PET imaging studies. Progression-free survival (PFS) and overall survival (OS) were compared between responders and nonresponders using Kaplan-Meier and log-rank analyses. Programmed cell death protein 1 ligand expression status was assessed, and its association with outcome was investigated. Results: Twenty-seven patients had 18F-FDG PET/CT imaging at baseline and after at least 4 cycles pembrolizumab. Median PFS and OS were 3.4 and 15.1 mo, respectively. Response rates were 7%, 7%, 30%, and 30% based on RECIST, modified RECIST, PERCISTSULpeak, and PERCISTMTV response criteria, respectively. Response according to PERCISTMTV predicted prolonged OS or PFS (P < 0.01), whereas all other imaging criteria and programmed cell death protein 1 ligand expression did not. Conclusion:18F-FDG PET metabolic volume response predicts survival in patients with malignant mesothelioma receiving high-dose pembrolizumab. These results should prompt inclusion of PET response assessment in future phase 3 clinical trials.

  © 2021 by the Society of Nuclear Medicine and Molecular Imaging.

• 18F-FDG PET Assessment of Malignant Pleural Mesothelioma: Total Lesion Volume and Total Lesion Glycolysis-The Central Role of Volume. J.C. Reynolds, R. Maass-Moreno, A. Thomas, et al. 2020;61(11):1570-1575. PubMed · Publisher · Free full text

  Abstract

  Cancer survival is related to tumor volume. 18F-FDG PET measurement of tumor volume holds promise but is not yet a clinical tool. Measurements come in 2 forms: the first is total lesion volume (TLV) based on the number of voxels in the tumor, and the second is total lesion glycolysis (TLG), which is the TLV multiplied by the average SUL (i.e., SUV normalized for lean mass) of the tumor (SULaverage). In this study, we measured tumor volume in patients with malignant pleural mesothelioma (MPM). Methods: A threshold-based program in Interactive Data Language was developed to measure tumor volume in 18F-FDG PET images. Nineteen patients with MPM were studied before and after 2 cycles (6 wk) of chemoimmunotherapy. Measurements included TLV, TLG, the sum of the SULs in the tumor (SULtotal, a measure of total 18F-FDG uptake), and SULaverageResults: Baseline TLV ranged from 11 to 2,610 cm3 TLG ranged from 32 to 8,552 cm3 g/mL and correlated strongly with TLV. Although tumor volumes ranged over 3 orders of magnitude, SULaverage stayed within a narrow range of 2.4-5.3 units. Thus, TLV was the major component of TLG, whereas SULaverage was a minor component and was essentially constant. Further evaluation of SULaverage showed that in this cohort its 2 components, SULtotal and TLV, changed in parallel and were strongly correlated (r = 0.99, P < 0.01). Thus, whether the tumors were large or small, 18F-FDG uptake as measured by SULtotal was proportional to the TLV. Conclusion: TLG equals TLV multiplied by SULaverage, essentially TLV multiplied by a constant. Thus TLG, commonly considered a measure of metabolic activity in tumors, is also in this cohort a measure of tumor volume. The constancy of SULaverage is due to the fact that 18F-FDG uptake is proportional to tumor volume. Thus, in this study, 18F-FDG uptake was also a measure of volume.

  © 2020 by the Society of Nuclear Medicine and Molecular Imaging.

2010s

• Synergistic Effect of a Mesothelin-Targeted 227Th Conjugate in Combination with DNA Damage Response Inhibitors in Ovarian Cancer Xenograft Models. K. Wickstroem, U.B. Hagemann, V. Cruciani, et al. 2019;60(9):1293-1300. PubMed · Publisher · Free full text

  Abstract

  Targeted 227Th conjugates (TTCs) represent a new class of therapeutic radiopharmaceuticals for targeted α-therapy. They comprise the α-emitter 227Th complexed to a 3,2-hydroxypyridinone chelator conjugated to a tumor-targeting monoclonal antibody. The high energy and short range of the α-particles induce antitumor activity, driven by the induction of complex DNA double-strand breaks. We hypothesized that blocking the DNA damage response (DDR) pathway should further sensitize cancer cells by inhibiting DNA repair, thereby increasing the response to TTCs. Methods: This article reports the evaluation of the mesothelin (MSLN)-TTC conjugate (BAY 2287411) in combination with several DDR inhibitors, each of them blocking different DDR pathway enzymes. MSLN is a validated cancer target known to be overexpressed in mesothelioma, ovarian, lung, breast, and pancreatic cancer, with low expression in normal tissue. In vitro cytotoxicity experiments were performed on cancer cell lines by combining the MSLN-TTC with inhibitors of ataxia telangiectasia mutated, ataxia telangiectasia and Rad3-related (ATR), DNA-dependent protein kinase, and poly[adenosine diphosphate ribose] polymerase (PARP) 1/2. Further, we evaluated the antitumor efficacy of the MSLN-TTC in combination with DDR inhibitors in human ovarian cancer xenograft models. Results: Synergistic activity was observed in vitro for all tested inhibitors (inhibitors are denoted herein by the suffix "i") when combined with MSLN-TTC. ATRi and PARPi appeared to induce the strongest increase in potency. Further, in vivo antitumor efficacy of the MSLN-TTC in combination with ATRi or PARPi was investigated in the OVCAR-3 and OVCAR-8 xenograft models in nude mice, demonstrating synergistic antitumor activity for the ATRi combination at doses demonstrated to be nonefficacious when administered as monotherapy. Conclusion: The presented data support the mechanism-based rationale for combining the MSLN-TTC with DDR inhibitors as new treatment strategies in MSLN-positive ovarian cancer.

  © 2019 by the Society of Nuclear Medicine and Molecular Imaging.

2000s

• From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. R.L. Wahl, H. Jacene, Y. Kasamon, et al. 2009;50 Suppl 1(Suppl 1):122S-50S. Review PubMed · Publisher · Free full text

  Abstract

  Unlabelled: The purpose of this article is to review the status and limitations of anatomic tumor response metrics including the World Health Organization (WHO) criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This article also reviews qualitative and quantitative approaches to metabolic tumor response assessment with (18)F-FDG PET and proposes a draft framework for PET Response Criteria in Solid Tumors (PERCIST), version 1.0.

  Methods: PubMed searches, including searches for the terms RECIST, positron, WHO, FDG, cancer (including specific types), treatment response, region of interest, and derivative references, were performed. Abstracts and articles judged most relevant to the goals of this report were reviewed with emphasis on limitations and strengths of the anatomic and PET approaches to treatment response assessment. On the basis of these data and the authors' experience, draft criteria were formulated for PET tumor response to treatment.

  Results: Approximately 3,000 potentially relevant references were screened. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely applied but still has limitations in response assessments. For example, despite effective treatment, changes in tumor size can be minimal in tumors such as lymphomas, sarcoma, hepatomas, mesothelioma, and gastrointestinal stromal tumor. CT tumor density, contrast enhancement, or MRI characteristics appear more informative than size but are not yet routinely applied. RECIST criteria may show progression of tumor more slowly than WHO criteria. RECIST 1.1 criteria (assessing a maximum of 5 tumor foci, vs. 10 in RECIST) result in a higher complete response rate than the original RECIST criteria, at least in lymph nodes. Variability appears greater in assessing progression than in assessing response. Qualitative and quantitative approaches to (18)F-FDG PET response assessment have been applied and require a consistent PET methodology to allow quantitative assessments. Statistically significant changes in tumor standardized uptake value (SUV) occur in careful test-retest studies of high-SUV tumors, with a change of 20% in SUV of a region 1 cm or larger in diameter; however, medically relevant beneficial changes are often associated with a 30% or greater decline. The more extensive the therapy, the greater the decline in SUV with most effective treatments. Important components of the proposed PERCIST criteria include assessing normal reference tissue values in a 3-cm-diameter region of interest in the liver, using a consistent PET protocol, using a fixed small region of interest about 1 cm(3) in volume (1.2-cm diameter) in the most active region of metabolically active tumors to minimize statistical variability, assessing tumor size, treating SUV lean measurements in the 1 (up to 5 optional) most metabolically active tumor focus as a continuous variable, requiring a 30% decline in SUV for "response," and deferring to RECIST 1.1 in cases that do not have (18)F-FDG avidity or are technically unsuitable. Criteria to define progression of tumor-absent new lesions are uncertain but are proposed.

  Conclusion: Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria have limitations, particularly in assessing the activity of newer cancer therapies that stabilize disease, whereas (18)F-FDG PET appears particularly valuable in such cases. The proposed PERCIST 1.0 criteria should serve as a starting point for use in clinical trials and in structured quantitative clinical reporting. Undoubtedly, subsequent revisions and enhancements will be required as validation studies are undertaken in varying diseases and treatments.

1980s

• Gallium-67 uptake in the lung of asbestos exposed sheep: early association with enhanced macrophage-derived fibronectin accumulation. R. Bégin, G. Bisson, R. Lambert, et al. 1986;27(4):538-44. PubMed

  Abstract

  To evaluate the time course and mechanisms of enhanced 67Ga lung uptake in asbestosis, we exposed two groups of sheep every 2 wk to either 100 ml saline (controls) or 100 mg UICC chrysotile fibers in 100 ml saline. The sheep were evaluated periodically by pulmonary function tests (PFT), thoracic radiograph (TR), 67Ga lung scan bronchoalveolar lavage (BAL), and transbronchial lung biopsy (TLB). By month 24 of the study, 9/15 exposed sheep had developed the initial alveolitis and had significant changes in PFT, TR, and TLB. The other six exposed sheep differed from controls only by a 75% increase in BAL fibronectin until month 30, where significant changes in albumin occurred and 67Ga scan score increased. The nine sheep with alveolitis had significant sustained increases in 67Ga scan and BAL levels from month 6, associated with a 150% increase in BAL fibronectin and other parameters of disease activity changed from month 18 to 30. We concluded that in the sheep model of asbestosis, significant changes in 67Ga scan, 67Ga BAL counts, and excessive elevation of BAL fibronectin preceded other parameters of disease activity. The data suggest that excessively activated macrophages are primarily responsible for the early 67Ga lung uptake.

• Gallium-67 thoracic scan and pleural disease in asbestos workers. R. Lambert, G. Bisson, G. Lamoureux, et al. 1985;26(6):600-3. PubMed

  Abstract

  We have recently reported that 67Ga scanning in asbestos workers can document excessive uptake of the marker among workers without sufficient criteria for asbestosis, but in our initial report we could not exclude definitely that 67Ga uptake could be related to pleural disease. To further test this hypothesis, we analyzed the 67Ga thoracic scan in relation to profusion scores of pleural disease on chest roentgenogram and CT scan of the thorax in 171 asbestos workers. We found no significant correlation between the 67Ga lung uptake and the radiographic scores of pleural disease. We concluded that pleural plaques are not an active site of 67Ga accumulation and do not contribute significantly to the thoracic uptake of the marker.

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