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{"title":"Pharmacokinetic Comparison of Selective Prostatic Arterial and Intravenous PSMA PET/CT Radioligand Infusions in Primary Prostatic Adenocarcinoma.","authors":"Ryan Kohlbrenner, Xiao Wu, Hao G Nguyen, Matthew R Cooperberg, Tushar Chakravarty, Peter R Carroll, Thomas A Hope","doi":"10.1148/radiol.232544","DOIUrl":null,"url":null,"abstract":"<p><p>Background Intravenous prostate-specific membrane antigen (PSMA)-targeted radioligand therapy improves survival in men with metastatic castration-resistant prostate cancer. Yet, the impact of selective prostatic arterial administration on primary tumor uptake is unclear. Purpose To compare gallium 68 (<sup>68</sup>Ga)-PSMA-11 uptake using dynamic PET/CT in prostatic tumoral volumes of interest (VOIs) during intravenous and selective prostatic arterial infusions for individuals with untreated, high-risk prostate cancer. Materials and Methods In this prospective, intraindividual comparative study conducted at an academic medical center, five men aged 58, 61, 64, 66, and 68 years with treatment-naive prostate cancer were enrolled between January 2022 and February 2023 and underwent two dynamic <sup>68</sup>Ga-PSMA-11 PET/CT examinations 1 week apart. During the first examination, the radiotracer was administered intravenously. During the second administration, the radiotracer was delivered into either the right or left prostatic artery through an angiographically placed microcatheter. The primary outcome was maximum standardized uptake value (SUV<sub>max</sub>) in prostatic tumoral VOIs. The secondary outcomes included mean SUV (SUV<sub>mean</sub>) in prostatic tumoral VOIs and area under the SUV<sub>mean</sub> curves (AUC). Longitudinal mixed-effects models were used to compare dynamic SUV<sub>max</sub> and SUV<sub>mean</sub> time-activity curves (TACs), and paired <i>t</i> tests were used for the remaining data. Results The mean SUV<sub>max</sub> within tumoral VOIs was 14 (range, 3-43) for venous sessions and 938 (range, 460-1436) for arterial sessions (<i>P</i> = .008). The SUV<sub>mean</sub> within VOIs was greater during arterial sessions (<i>P</i> < .001) overall and 46-fold and 19-fold greater at peak uptake and final time points, respectively. The mean AUC was greater on arterial TACs than on venous TACs at 14600 SUV × min (range, 8353-20025 SUV × min) and 240 SUV × min (range, 69-622 SUV × min), respectively (<i>P</i> = .002). Conclusion Selective prostatic arterial infusion resulted in greater <sup>68</sup>Ga-PSMA-11 tumoral SUV than intravenous infusion. Further study of local-regional, intra-arterial delivery of a PSMA-targeted theranostic agent is warranted in high-risk prostate cancer. ClinicalTrials.gov identifier: NCT04976257 © RSNA, 2024 <i>Supplemental material is available for this article.</i> See also the editorial by Civelek in this issue.</p>","PeriodicalId":20896,"journal":{"name":"Radiology","volume":null,"pages":null},"PeriodicalIF":12.1000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11366670/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Radiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1148/radiol.232544","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
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Abstract
Background Intravenous prostate-specific membrane antigen (PSMA)-targeted radioligand therapy improves survival in men with metastatic castration-resistant prostate cancer. Yet, the impact of selective prostatic arterial administration on primary tumor uptake is unclear. Purpose To compare gallium 68 (68 Ga)-PSMA-11 uptake using dynamic PET/CT in prostatic tumoral volumes of interest (VOIs) during intravenous and selective prostatic arterial infusions for individuals with untreated, high-risk prostate cancer. Materials and Methods In this prospective, intraindividual comparative study conducted at an academic medical center, five men aged 58, 61, 64, 66, and 68 years with treatment-naive prostate cancer were enrolled between January 2022 and February 2023 and underwent two dynamic 68 Ga-PSMA-11 PET/CT examinations 1 week apart. During the first examination, the radiotracer was administered intravenously. During the second administration, the radiotracer was delivered into either the right or left prostatic artery through an angiographically placed microcatheter. The primary outcome was maximum standardized uptake value (SUVmax ) in prostatic tumoral VOIs. The secondary outcomes included mean SUV (SUVmean ) in prostatic tumoral VOIs and area under the SUVmean curves (AUC). Longitudinal mixed-effects models were used to compare dynamic SUVmax and SUVmean time-activity curves (TACs), and paired t tests were used for the remaining data. Results The mean SUVmax within tumoral VOIs was 14 (range, 3-43) for venous sessions and 938 (range, 460-1436) for arterial sessions (P = .008). The SUVmean within VOIs was greater during arterial sessions (P < .001) overall and 46-fold and 19-fold greater at peak uptake and final time points, respectively. The mean AUC was greater on arterial TACs than on venous TACs at 14600 SUV × min (range, 8353-20025 SUV × min) and 240 SUV × min (range, 69-622 SUV × min), respectively (P = .002). Conclusion Selective prostatic arterial infusion resulted in greater 68 Ga-PSMA-11 tumoral SUV than intravenous infusion. Further study of local-regional, intra-arterial delivery of a PSMA-targeted theranostic agent is warranted in high-risk prostate cancer. ClinicalTrials.gov identifier: NCT04976257 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Civelek in this issue.
原发性前列腺腺癌选择性前列腺动脉灌注与静脉 PSMA PET/CT 放射性配体灌注的药代动力学比较
背景 静脉注射前列腺特异性膜抗原(PSMA)靶向放射性配体疗法可提高转移性阉割耐药前列腺癌男性患者的生存率。然而,选择性前列腺动脉给药对原发肿瘤摄取的影响尚不清楚。目的 比较未经治疗的高危前列腺癌患者在静脉输注和选择性前列腺动脉输注期间前列腺肿瘤感兴趣容积(VOI)中使用动态 PET/CT 对 68 (68Ga) -PSMA-11 镓的摄取情况。材料与方法 在这项前瞻性、个体内部比较研究中,一家学术医疗中心在 2022 年 1 月至 2023 年 2 月期间招募了五名年龄分别为 58、61、64、66 和 68 岁的前列腺癌患者,并对他们进行了两次动态 68Ga-PSMA-11 PET/CT 检查,每次检查间隔一周。第一次检查时,通过静脉注射放射性示踪剂。第二次给药时,通过血管造影置入的微导管将放射性示踪剂送入右侧或左侧前列腺动脉。主要结果是前列腺肿瘤VOI的最大标准化摄取值(SUVmax)。次要结果包括前列腺肿瘤VOI的平均SUV(SUVmean)和SUVmean曲线下面积(AUC)。采用纵向混合效应模型比较动态 SUVmax 和 SUVmean 时间-活动曲线(TAC),其余数据采用配对 t 检验。结果 静脉疗程的肿瘤 VOI 内平均 SUVmax 为 14(范围:3-43),动脉疗程的肿瘤 VOI 内平均 SUVmax 为 938(范围:460-1436)(P = .008)。总体而言,动脉疗程中 VOIs 内的 SUV 平均值更大(P < .001),摄取峰值和最后时间点的 SUV 平均值分别是静脉疗程的 46 倍和 19 倍。动脉 TAC 的平均 AUC 值大于静脉 TAC,分别为 14600 SUV × min(范围为 8353-20025 SUV × min)和 240 SUV × min(范围为 69-622 SUV × min)(P = .002)。结论 与静脉输注相比,选择性前列腺动脉输注可获得更大的 68Ga-PSMA-11 肿瘤 SUV。在高风险前列腺癌中,有必要对局部区域动脉内注射 PSMA 靶向治疗剂进行进一步研究。ClinicalTrials.gov 标识符:NCT04976257 © RSNA, 2024 本文有补充材料。另请参阅本期 Civelek 的社论。
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