Daniele Bertoglio, Alison R Weiss, William Liguore, Lauren Drew Martin, Theodore Hobbs, John Templon, Sathya Srinivasan, Celia Dominguez, Ignacio Munoz-Sanjuan, Vinod Khetarpal, Jeroen Verhaeghe, Steven Staelens, Jeanne Link, Longbin Liu, Jonathan A Bard, Jodi L McBride
{"title":"In Vivo Cerebral Imaging of Mutant Huntingtin Aggregates Using <sup>11</sup>C-CHDI-180R PET in a Nonhuman Primate Model of Huntington Disease.","authors":"Daniele Bertoglio, Alison R Weiss, William Liguore, Lauren Drew Martin, Theodore Hobbs, John Templon, Sathya Srinivasan, Celia Dominguez, Ignacio Munoz-Sanjuan, Vinod Khetarpal, Jeroen Verhaeghe, Steven Staelens, Jeanne Link, Longbin Liu, Jonathan A Bard, Jodi L McBride","doi":"10.2967/jnumed.123.265569","DOIUrl":"10.2967/jnumed.123.265569","url":null,"abstract":"<p><p>Huntington disease (HD) is a neurodegenerative disorder caused by an expanded polyglutamine (CAG) trinucleotide expansion in the huntingtin (<i>HTT</i>) gene that encodes the mutant huntingtin protein (mHTT). Visualization and quantification of cerebral mHTT will provide a proxy for target engagement and a means to evaluate therapeutic interventions aimed at lowering mHTT in the brain. Here, we validated the novel radioligand <sup>11</sup>C-labeled 6-(5-((5-methoxypyridin-2-yl)methoxy)benzo[d]oxazol-2-yl)-2-methylpyridazin-3(2H)-one (<sup>11</sup>C-CHDI-180R) using PET imaging to quantify cerebral mHTT aggregates in a macaque model of HD. <b>Methods:</b> Rhesus macaques received MRI-guided intrastriatal delivery of a mixture of AAV2 and AAV2.retro viral vectors expressing an HTT fragment bearing 85 CAG repeats (85Q, <i>n</i> = 5), a control HTT fragment bearing 10 CAG repeats (10Q, <i>n</i> = 4), or vector diluent only (phosphate-buffered saline, <i>n</i> = 5). Thirty months after surgery, 90-min dynamic PET/CT imaging was used to investigate <sup>11</sup>C-CHDI-180R brain kinetics, along with serial blood sampling to measure input function and stability of the radioligand. The total volume of distribution was calculated using a 2-tissue-compartment model as well as Logan graphical analysis for regional quantification. Immunostaining for mHTT was performed to corroborate the in vivo findings. <b>Results:</b> <sup>11</sup>C-CHDI-180R displayed good metabolic stability (51.4% ± 4.0% parent in plasma at 60 min after injection). Regional time-activity curves displayed rapid uptake and reversible binding, which were described by a 2-tissue-compartment model. Logan graphical analysis was associated with the 2-tissue-compartment model (<i>r</i> <sup>2</sup> = 0.96, <i>P</i> < 0.0001) and used to generate parametric volume of distribution maps. Compared with controls, animals administered the 85Q fragment exhibited significantly increased <sup>11</sup>C-CHDI-180R binding in several cortical and subcortical brain regions (group effect, <i>P</i> < 0.0001). No difference in <sup>11</sup>C-CHDI-180R binding was observed between buffer and 10Q animals. The presence of mHTT aggregates in the 85Q animals was confirmed histologically. <b>Conclusion:</b> We validated <sup>11</sup>C-CHDI-180R as a radioligand to visualize and quantify mHTT aggregated species in a HD macaque model. These findings corroborate our previous work in rodent HD models and show that <sup>11</sup>C-CHDI-180R is a promising tool to assess the mHTT aggregate load and the efficacy of therapeutic strategies.</p>","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":" ","pages":"1581-1587"},"PeriodicalIF":9.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10018205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benedict Edward Mc Larney, Mijin Kim, Sheryl Roberts, Magdalena Skubal, Hsiao-Ting Hsu, Anuja Ogirala, Edwin C Pratt, Naga Vara Kishore Pillarsetty, Daniel A Heller, Jason S Lewis, Jan Grimm
{"title":"Ambient Light Resistant Shortwave Infrared Fluorescence Imaging for Preclinical Tumor Delineation via the pH Low-Insertion Peptide Conjugated to Indocyanine Green.","authors":"Benedict Edward Mc Larney, Mijin Kim, Sheryl Roberts, Magdalena Skubal, Hsiao-Ting Hsu, Anuja Ogirala, Edwin C Pratt, Naga Vara Kishore Pillarsetty, Daniel A Heller, Jason S Lewis, Jan Grimm","doi":"10.2967/jnumed.123.265686","DOIUrl":"10.2967/jnumed.123.265686","url":null,"abstract":"<p><p>Shortwave infrared (900-1,700 nm) fluorescence imaging (SWIRFI) has shown significant advantages over visible (400-650 nm) and near-infrared (700-900 nm) fluorescence imaging (reduced autofluorescence, improved contrast, tissue resolution, and depth sensitivity). However, there is a major lag in the clinical translation of preclinical SWIRFI systems and targeted SWIRFI probes. <b>Methods:</b> We preclinically show that the pH low-insertion peptide conjugated to indocyanine green (pHLIP ICG), currently in clinical trials, is an excellent candidate for cancer-targeted SWIRFI. <b>Results:</b> pHLIP ICG SWIRFI achieved picomolar sensitivity (0.4 nM) with binary and unambiguous tumor screening and resection up to 96 h after injection in an orthotopic breast cancer mouse model. SWIRFI tumor screening and resection had ambient light resistance (possible without gating or filtering) with outstanding signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values at exposures from 10 to 0.1 ms. These SNR and CNR values were also found for the extended emission of pHLIP ICG in vivo (>1,100 nm, 300 ms). <b>Conclusion:</b> SWIRFI sensitivity and ambient light resistance enabled continued tracer clearance tracking with unparalleled SNR and CNR values at video rates for tumor delineation (achieving a tumor-to-muscle ratio above 20). In total, we provide a direct precedent for the democratic translation of an ambient light resistant SWIRFI and pHLIP ICG ecosystem, which can instantly improve tumor resection.</p>","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":" ","pages":"1647-1653"},"PeriodicalIF":9.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10068808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emma L Brown, Shayla Shmuel, Komal Mandleywala, Sandeep Surendra Panikar, Na-Keysha Berry, Yi Rao, Abbey Zidel, Jason S Lewis, Patrícia M R Pereira
{"title":"Immuno-PET Detects Antibody-Drug Potency on Coadministration with Statins.","authors":"Emma L Brown, Shayla Shmuel, Komal Mandleywala, Sandeep Surendra Panikar, Na-Keysha Berry, Yi Rao, Abbey Zidel, Jason S Lewis, Patrícia M R Pereira","doi":"10.2967/jnumed.122.265172","DOIUrl":"10.2967/jnumed.122.265172","url":null,"abstract":"<p><p>The human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) are antibody-drug conjugates (ADC) clinically used to treat HER2-positive breast cancer, with the latter receiving clinical approval in 2021 for HER2-positive gastric cancer. Lovastatin, a cholesterol-lowering drug, temporally elevates cell-surface HER2 in ways that enhance HER2-ADC binding and internalization. <b>Methods:</b> In an NCIN87 gastric xenograft model and a gastric patient-derived xenograft model, we used the <sup>89</sup>Zr-labeled or <sup>64</sup>Cu-labeled anti-HER2 antibody trastuzumab to investigate the dosing regimen of ADC therapy with and without coadministration of lovastatin. We compared the ADC efficacy of a multiple-dose ADC regime, which replicates the clinical dose regimen standard, with a single-dose regime. <b>Results:</b> T-DM1/lovastatin treatment inhibited tumor growth, regardless of multiple- or single-dose T-DM1 administration. Coadministration of lovastatin with T-DM1 or T-DXd as a single dose enhanced tumor growth inhibition, which was accompanied by a decrease in signal on HER2-targeted immuno-PET and a decrease in HER2-mediated signaling at the cellular level. DNA damage signaling was increased on ADC treatment in vitro. <b>Conclusion:</b> Our data from a gastric cancer xenograft show the utility of HER2-targeted immuno-PET to inform the tumor response to ADC therapies in combination with modulators of cell-surface target availability. Our studies also demonstrate that statins enhance ADC efficacy in both a cell-line and a patient-derived xenograft model in ways that enable a single-dose administration of the ADC.</p>","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":" ","pages":"1638-1646"},"PeriodicalIF":9.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9698302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wolfgang Andreas Weber, Henryk Barthel, Frank M Bengel, Matthias M Eiber, Ken Herrmann, Michael Schäfers
{"title":"Reply to: Not All Gatekeepers Are Theranostics.","authors":"Wolfgang Andreas Weber, Henryk Barthel, Frank M Bengel, Matthias M Eiber, Ken Herrmann, Michael Schäfers","doi":"10.2967/jnumed.123.266028","DOIUrl":"10.2967/jnumed.123.266028","url":null,"abstract":"TO THE EDITOR: Sometimes we need to challenge the views of colleagues and friends, especially when their thinking has the effect of muddying the waters rather than providing greater insight and clarity. I believe this to be the case with the opinion piece by Weber et al. in the May 2023 issue of the journal (1). The authors seek to redefine the term theranostic. They assert that this is any molecular imaging probe that provides actionable information for any subsequent therapeutic. This includes medical therapies, radiation therapy, surgery, or cell therapies. I believe that, in doing so, they are losing the very essence of what a theranostic is. I agree with the authors that the therapeutic component of a theranostic pair need not be a radionuclide therapy, but I contend that it mustbe the same(oravery similar)moleculeormoiety. It couldbecarrying a toxic therapeutic or it may be an antibody that targets a protein (e.g., amyloid in the brain), but it has to be the same targeting moiety. What the authors of this article are referring to as a theranostic imaging probe when used with a range of other therapies is more accurately described by the term gatekeeper or companion diagnostic. The imaging study validates the use of a certain therapeutic approach: this is not theranostics but simply a good use of medical imaging. The authors surely would not contend that a ventilation–perfusion lung scan demonstrating a pulmonary embolism that was subsequently treated with anticoagulation was a theranostic approach. Definitions are important and help us to describe and conceptualize the strategy chosen to diagnose and treat diseases. Seeking to dilute the definition of a theranostic in the way the authors have done will have the effect of confusing the basis of the concept and will be unhelpful. The theranostic approach is an extremely powerful one and should be amajor focus of future developments inmolecular imaging and therapy. We need to keep the concepts clear and appreciate the differences between gatekeeper and theranostic approaches. They are both very important, but they are not the same. Not all gatekeepers are theranostics.","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":" ","pages":"1662-1663"},"PeriodicalIF":9.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9698304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John J Sunderland, Stephen A Graves, Dusty M York, Christine A Mundt, Twyla B Bartel
{"title":"Response to \"Critique and Discussion of 'Multicenter Evaluation of Frequency and Impact of Activity Infiltration in PET Imaging, Including Microscale Modeling of Skin-Absorbed Dose'\".","authors":"John J Sunderland, Stephen A Graves, Dusty M York, Christine A Mundt, Twyla B Bartel","doi":"10.2967/jnumed.123.266596","DOIUrl":"10.2967/jnumed.123.266596","url":null,"abstract":"SPECT/CT-based dosimetry study is already in preparation. Consequently, we saw no need to report preliminary results, which soon will become obsolete anyway. The other reason is the challenging interpretation of dosimetry data in predicting clinical consequences of systemic radioligand therapy. The latter issue is now addressed by Pretze et al., who mention various physical and radiation biologic aspects of this theme. We appreciate receiving such an instructive letter, stimulating a fruitful academic discussion. First, Pretze et al. mention further radionuclides that could serve as alternatives to Lu. Indeed, the amount of Yb that is needed for the production of high-specific-activity Lu without Lu impurities (half-life, 161 d) is limited. Consequently, the costs for producing no-carrier-added Lu are relatively high. Routine availability of Tb and Cu is currently even worse than for Lu. In contrast, Re is readily available from a well-established generator system and, if generators are eluted regularly, converts it into reduced radionuclide costs by approximately a power of 10. The current shortage of Lu-PSMA-617 in the United States (Pluvicto from Novartis has been on the Food and Drug Administration’s shortage list since March 7, 2023) illustrates the logistic challenges of airfreight delivery even between well-developed countries. In regions with a lower airport density, just-in-time delivery of Lu (half-life, 6.7 d) radiopharmaceuticals is likely an illusion, and the same applies to Tb (half-life, 6.9 d) and Cu (half-life, 2.6 d). Hence, the 70-d half-life of the W/Re generator is the most reasonable option to have local access to PSMA radioligand therapy at all. Next, the letter addresses the challenge of projecting absorbed doses based on small-animal studies to human beings. Hence, studies in pigs would be required. However, beyond radiation geometry, the specific expression of PSMA in the proximal kidney tubules has to be considered. A study comparing human PSMA with its rat and pig orthologs exhibits different glutamate carboxypeptidase II expression levels among the species studied (2). Therefore, we considered the theranostic approach a more responsible way to continue clinical development; that is, innocuous Tc-PSMA-GCK01 imaging will be used to extrapolate the dosimetry of RePSMA-GCK01 therapy in men. Pretze et al. estimated that the same activities of Re-PSMA may convert into a 1.7 times higher kidney dose but only a 51% absorbed dose to tumors with a mass of 10g when compared with LuPSMA-617. This is not too much away from our own preliminary approximation. However, because of its higher b-energy, Re theoretically performs better against larger tumor lesions (23–32mm) than does Lu (3). In a tumor model that is very similar to the typical clustered PSMA expression pattern in prostate cancer, the increased cross-fire effect of Re improved its intercluster microdosimetry (4). Pretze et al. emphasized that the antitumor activity of Re","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":" ","pages":"1664-1667"},"PeriodicalIF":9.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586484/pdf/jnumed.123.266596.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10552810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meiqi Wu, Yanyu Wang, Qiao Yang, Xuezhu Wang, Xu Yang, Haiqun Xing, Xinting Sang, Xiang Li, Haitao Zhao, Li Huo
{"title":"Comparison of Baseline <sup>68</sup>Ga-FAPI and <sup>18</sup>F-FDG PET/CT for Prediction of Response and Clinical Outcome in Patients with Unresectable Hepatocellular Carcinoma Treated with PD-1 Inhibitor and Lenvatinib.","authors":"Meiqi Wu, Yanyu Wang, Qiao Yang, Xuezhu Wang, Xu Yang, Haiqun Xing, Xinting Sang, Xiang Li, Haitao Zhao, Li Huo","doi":"10.2967/jnumed.123.265712","DOIUrl":"10.2967/jnumed.123.265712","url":null,"abstract":"<p><p>Fibroblast activation protein contributes to immunosuppression and resistance to immunotherapies. This study aimed to compare baseline <sup>68</sup>Ga-labeled fibroblast activation protein inhibitor (<sup>68</sup>Ga-FAPI) PET/CT and <sup>18</sup>F-FDG PET/CT in response and survival prediction in unresectable hepatocellular carcinoma (uHCC) patients treated with the combination of programmed cell death 1 (PD-1) inhibitor and lenvatinib. <b>Methods:</b> In this prospective cohort study, 22 patients with uHCC who underwent baseline <sup>18</sup>F-FDG and <sup>68</sup>Ga-FAPI PET/CT and soon began taking a combination of PD-1 inhibitor and lenvatinib were recruited. Semiquantitative indices of baseline PET/CT were measured as <sup>18</sup>F-FDG SUV<sub>max</sub>, metabolic tumor volume, total lesion glycolysis, <sup>68</sup>Ga-FAPI SUV<sub>max</sub>, <sup>68</sup>Ga-FAPI-avid tumor volume (FTV), and total lesion fibroblast activation protein expression (TLF). The primary endpoint was durable or nondurable clinical benefit after treatment, and the secondary endpoints were progression-free survival (PFS) and overall survival (OS). <b>Results:</b> The overall response rate of the combination therapy was 41% (9/22). Fifty percent of patients had durable clinical benefit. Median PFS and OS were 4.8 and 14.4 mo, respectively. Patients with nondurable clinical benefit showed a significantly higher FTV and TLF than those with durable clinical benefit, whereas <sup>18</sup>F-FDG parameters overlapped. A higher <sup>68</sup>Ga-FAPI-avid tumor burden (FTV > 230.46 cm<sup>3</sup> or TLF > 961.74 SUV<sub>body weight</sub>⋅cm<sup>3</sup>) predicted both shorter PFS (4.0 vs. 13.5 mo, <i>P</i> = 0.016) and shorter OS (7.8 mo vs. not reached, <i>P</i> = 0.030). Patients with a higher metabolic tumor burden (metabolic tumor volume > 206.80 cm<sup>3</sup> or total lesion glycolysis > 693.53 SUV<sub>body weight</sub>⋅cm<sup>3</sup>) showed a shorter OS although the difference did not reach statistical significance (<i>P</i> = 0.085). In multivariate analysis, a higher <sup>68</sup>Ga-FAPI-avid tumor burden (hazard ratio [HR], 3.88 [95% CI, 1.26-12.01]; <i>P</i> = 0.020) and macrovascular invasion (HR, 4.00 [95% CI, 1.06-15.14]; <i>P</i> = 0.039) independently predicted a shorter PFS, whereas a higher <sup>68</sup>Ga-FAPI-avid tumor burden (HR, 5.92 [95% CI, 1.19-29.42]; <i>P</i> = 0.035) and bone metastases (HR, 5.88 [95% CI, 1.33-25.93]; <i>P</i> = 0.022) independently predicted a shorter OS. <b>Conclusion:</b> Volumetric indices on baseline <sup>68</sup>Ga-FAPI PET/CT were potentially independent prognostic factors to predict durable clinical benefit, PFS, and OS in uHCC patients treated with a combination of PD-1 and lenvatinib. Baseline <sup>68</sup>Ga-FAPI PET/CT may facilitate uHCC patient selection before combination therapy.</p>","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":" ","pages":"1532-1539"},"PeriodicalIF":9.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9883568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexandre Larouze, Mario Alcocer-Ávila, Clément Morgat, Christophe Champion, Elif Hindié
{"title":"Membrane and Nuclear Absorbed Doses from <sup>177</sup>Lu and <sup>161</sup>Tb in Tumor Clusters: Effect of Cellular Heterogeneity and Potential Benefit of Dual Targeting-A Monte Carlo Study.","authors":"Alexandre Larouze, Mario Alcocer-Ávila, Clément Morgat, Christophe Champion, Elif Hindié","doi":"10.2967/jnumed.123.265509","DOIUrl":"10.2967/jnumed.123.265509","url":null,"abstract":"<p><p>Early use of targeted radionuclide therapy to eradicate tumor cell clusters and micrometastases might offer cure. However, there is a need to select appropriate radionuclides and assess the potential impact of heterogeneous targeting. <b>Methods:</b> The Monte Carlo code CELLDOSE was used to assess membrane and nuclear absorbed doses from <sup>177</sup>Lu and <sup>161</sup>Tb (β<sup>-</sup>-emitter with additional conversion and Auger electrons) in a cluster of 19 cells (14-μm diameter, 10-μm nucleus). The radionuclide distributions considered were cell surface, intracytoplasmic, or intranuclear, with 1,436 MeV released per labeled cell. To model heterogeneous targeting, 4 of the 19 cells were unlabeled, their position being stochastically determined. We simulated situations of single targeting, as well as dual targeting, with the 2 radiopharmaceuticals aiming at different targets. <b>Results:</b> <sup>161</sup>Tb delivered 2- to 6-fold higher absorbed doses to cell membranes and 2- to 3-fold higher nuclear doses than <sup>177</sup>Lu. When all 19 cells were targeted, membrane and nuclear absorbed doses were dependent mainly on radionuclide location. With cell surface location, membrane absorbed doses were substantially higher than nuclear absorbed doses, both with <sup>177</sup>Lu (38-41 vs. 4.7-7.2 Gy) and with <sup>161</sup>Tb (237-244 vs. 9.8-15.1 Gy). However, when 4 cells were not targeted by the cell surface radiopharmaceutical, the membranes of these cells received on average only 9.6% of the <sup>177</sup>Lu absorbed dose and 2.9% of the <sup>161</sup>Tb dose, compared with a cluster with uniform cell targeting, whereas the impact on nuclear absorbed doses was moderate. With an intranuclear radionuclide location, the nuclei of unlabeled cells received only 17% of the <sup>177</sup>Lu absorbed dose and 10.8% of the <sup>161</sup>Tb dose, compared with situations with uniform targeting. With an intracytoplasmic location, nuclear and membrane absorbed doses to unlabeled cells were one half to one quarter those obtained with uniform targeting, both for <sup>177</sup>Lu and for <sup>161</sup>Tb. Dual targeting was beneficial in minimizing absorbed dose heterogeneities. <b>Conclusion:</b> To eradicate tumor cell clusters, <sup>161</sup>Tb may be a better candidate than <sup>177</sup>Lu. Heterogeneous cell targeting can lead to substantial heterogeneities in absorbed doses. Dual targeting was helpful in reducing dose heterogeneity and should be explored in preclinical and clinical studies.</p>","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":" ","pages":"1619-1624"},"PeriodicalIF":9.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9995548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Johan S. Masjhur, dr, SpPD-KEMD, SpKN-TM, 1942-2023.","authors":"Hussein S Kartamihardja, Dale L Bailey","doi":"10.2967/jnumed.123.266196","DOIUrl":"10.2967/jnumed.123.266196","url":null,"abstract":"","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":" ","pages":"1669"},"PeriodicalIF":9.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10023600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Radiation Safety Considerations of Household Waste Disposal After Release of Patients Who Have Received [<sup>177</sup>Lu]Lu-PSMA-617.","authors":"Stephen A Graves","doi":"10.2967/jnumed.123.265750","DOIUrl":"10.2967/jnumed.123.265750","url":null,"abstract":"<p><p>Patients with metastatic prostate cancer are more likely than other groups to present for radiopharmaceutical therapy with urinary incontinence due to complications from prior local prostate cancer treatment. A consequence of urinary incontinence in patients receiving radiopharmaceutical therapy is the potential production of contaminated solid waste, which must be managed by the licensee and, at home, managed by and disposed of by the patient. Prolonging the patient stay in the treating facility after radiopharmaceutical therapy administration, until the first urinary void or potentially overnight, may moderately reduce the quantity of contaminated waste being managed by the patient at home. However, this approach does not fully mitigate the need for a patient waste-management strategy. In this brief communication, the relative radiation safety merits of contaminated waste disposal in the normal household waste stream in comparison to other waste management strategies are evaluated.</p>","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":" ","pages":"1567-1569"},"PeriodicalIF":9.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10037946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jan J Duin, Hilda A de Barros, Maarten L Donswijk, Eva E Schaake, Tim M van der Sluis, Esther M K Wit, Fijs W B van Leeuwen, Pim J van Leeuwen, Henk G van der Poel
{"title":"The Diagnostic Value of the Sentinel Node Procedure to Detect Occult Lymph Node Metastases in PSMA PET/CT Node-Negative Prostate Cancer Patients.","authors":"Jan J Duin, Hilda A de Barros, Maarten L Donswijk, Eva E Schaake, Tim M van der Sluis, Esther M K Wit, Fijs W B van Leeuwen, Pim J van Leeuwen, Henk G van der Poel","doi":"10.2967/jnumed.123.265556","DOIUrl":"10.2967/jnumed.123.265556","url":null,"abstract":"<p><p>Our objective was to assess the diagnostic value of the sentinel node (SN) procedure for lymph node staging in primary intermediate- and high-risk prostate cancer patients with node-negative results on prostate-specific membrane antigen PET/CT (miN0). <b>Methods:</b> From 2016 to 2022, 154 patients with primary, miN0 PCa were retrospectively included. All patients had a Briganti nomogram-assessed nodal risk of more than 5% and underwent a robot-assisted SN procedure for nodal staging. The prevalence of nodal metastases at histopathology and the occurrence of surgical complications according to the Clavien-Dindo classification were evaluated. <b>Results:</b> The SN procedure yielded 84 (14%) tumor-positive lymph nodes with a median metastasis size of 3 mm (interquartile range, 1-4 mm). In total, 55 patients (36%) were reclassified as pN1. A complication of Clavien-Dindo grade 3 or higher occured in 1 patient (0.6%). <b>Conclusion:</b> The SN procedure classified 36% of patients with miN0 prostate cancer with an elevated risk of nodal metastases as pN1.</p>","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":" ","pages":"1563-1566"},"PeriodicalIF":9.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9758673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}