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C-X-C Motif Chemokine Receptor 4-Directed Scintigraphy Using [99mTc]Tc-Pentixatec in Primary Aldosteronism: A Proof-of-Concept Study. 使用 [99mTc]Tc-Pentixatec 对原发性醛固酮增多症进行 C-X-C Motif 趋化因子受体 4 定向闪烁成像:概念验证研究
Pub Date : 2024-10-01 DOI: 10.2967/jnumed.124.268169
Johanna S Enke, Kathrin Ritzel, Evelyn Asbach, Nic G Reitsam, Bruno Märkl, Thomas Knösel, Denise Brüdgam, Malte Kircher, Christian H Pfob, Ralph A Bundschuh, Andreas Rinscheid, Bernd Nittbaur, Georgine Wienand, Margret Schottelius, Martin Reincke, Constantin Lapa, Alexander Dierks

C-X-C motif chemokine receptor 4 (CXCR4)-directed imaging has gained clinical interest in aiding clinical diagnostics in primary aldosteronism (PA). We retrospectively evaluated the feasibility of CXCR4-directed scintigraphy using the novel CXCR-4 ligand [99mTc]Tc-pentixatec in patients with PA. Methods: Six patients (mean age ± SD, 49 ± 15 y) underwent CXCR4-directed scintigraphy (including planar imaging and SPECT/CT) 30, 120, and 240 min after injection of 435 ± 50 MBq of [99mTc]Tc-pentixatec. Adrenal CXCR4 expression was analyzed by calculating lesion-to-contralateral ratios (LCRs). Imaging results were correlated to clinical information. Histopathology and clinical follow-up served as the standard of reference. Results: Three subjects showed lateralization of adrenal tracer accumulation, with a mean maximum lesion-to-contralateral ratio of 1.65 (range, 1.52-1.70), which correlated with morphologic findings on CT. One individual underwent adrenalectomy and presented with complete biochemical and clinical remission at follow-up. Histopathologic workup confirmed unilateral aldosterone-producing adenoma. Conclusion: [99mTc]Tc-pentixatec scintigraphy with SPECT in patients with PA is feasible and might offer a valuable alternative to CXCR4-directed imaging with [68Ga]Ga-pentixafor PET.

C-X-C motif趋化因子受体4(CXCR4)导向成像在原发性醛固酮增多症(PA)的临床诊断中获得了临床关注。我们使用新型 CXCR-4 配体 [99mTc]Tc-pentixatec 对 PA 患者进行了 CXCR4 定向闪烁成像的可行性回顾性评估。方法:六名患者(平均年龄 ± SD,49 ± 15 岁)在注射 435 ± 50 MBq [99mTc]Tc-pentixatec 后 30、120 和 240 分钟接受了 CXCR4 定向闪烁照相术(包括平面成像和 SPECT/CT)。通过计算病变与对侧比率(LCR)分析肾上腺CXCR4的表达。成像结果与临床信息相关联。组织病理学和临床随访作为参考标准。结果:三名受试者出现了肾上腺示踪剂侧向积聚,病灶与对侧比值平均最大值为 1.65(范围为 1.52-1.70),这与 CT 的形态学结果相关。其中一人接受了肾上腺切除术,随访时生化和临床症状完全缓解。组织病理学检查证实为单侧醛固酮腺瘤。结论在 PA 患者中使用 SPECT 进行[99mTc]Tc-pentixatec 闪烁显像是可行的,而且可能是[68Ga]Ga-pentixafor PET 进行 CXCR4 定向显像的一种有价值的替代方法。
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引用次数: 0
Is ChatGPT a Reliable Ghostwriter? ChatGPT 是可靠的鬼才吗?
Pub Date : 2024-10-01 DOI: 10.2967/jnumed.124.268341
Irène Buvat, Wolfgang A Weber
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引用次数: 0
Composite Prediction Score to Interpret Bone Focal Uptake in Hormone-Sensitive Prostate Cancer Patients Imaged with [18F]PSMA-1007 PET/CT. 用[18F]PSMA-1007 PET/CT 对激素敏感的前列腺癌患者骨灶摄取进行综合预测评分。
Pub Date : 2024-10-01 DOI: 10.2967/jnumed.124.267751
Matteo Bauckneht, Francesca D'Amico, Domenico Albano, Michele Balma, Camilla Cabrini, Francesco Dondi, Tania Di Raimondo, Virginia Liberini, Luca Sofia, Simona Peano, Mattia Riondato, Giuseppe Fornarini, Riccardo Laudicella, Luca Carmisciano, Egesta Lopci, Roberta Zanca, Marcello Rodari, Stefano Raffa, Maria Isabella Donegani, Daniela Dubois, Leonardo Peñuela, Cecilia Marini, Francesco Bertagna, Alberto Papaleo, Silvia Morbelli, Gianmario Sambuceti, Marta Ponzano, Alessio Signori

Unspecific bone uptake (UBU) related to [18F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [18F]PSMA-1007 bone focal uptake, aiding in result interpretation. Methods: We retrospectively analyzed [18F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUVmax, SUVmean, PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HUmean) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less (n = 2) or more (n = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake (n = 178) as PCa metastases or not. Results: In total, 448 bone [18F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT (P < 0.001) with determination of SUVmax (P < 0.001) and HUmean (P < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation (n = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score's AUC was significantly higher than that of HUmean (AUC, 0.62) and remained high among lesions with HUmean in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, P < 0.001). Conclusion: The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [18F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging.

与[18F]PSMA-1007 PET/CT 成像相关的非特异性骨摄取(UBU)是一项临床挑战。我们的目的是评估临床、生化和成像参数的组合能否预测[18F]PSMA-1007骨局灶摄取患者的骨骼转移,从而帮助解释结果。方法:我们回顾性分析了 3 家三级癌症中心对激素敏感型前列腺癌(PCa)患者进行的[18F]PSMA-1007 PET/CT 检查。第四个中心参与了外部验证。使用阈值法提取 SUVmax、SUVmean、PSMA 肿瘤体积和病变 PSMA 总量,分别绘制感兴趣体积。将相同的感兴趣体积应用于 CT 图像,以计算平均 Hounsfield 单位(HUmean)和最大 Hounsfield 单位。临床和实验室数据来自电子病历。综合参考标准包括随访组织病理学、生物化学和成像数据,用于区分 PCa 骨转移和 UBU。要求经验较少(n = 2)或经验较多(n = 2)的 PET 阅读器在参考标准的掩蔽下,以目测的方式评定病灶骨摄取(n = 178)是否为 PCa 转移。结果:总共在 267 名 PCa 患者中发现了 448 个骨[18F]PSMA-1007 局灶摄取标本。在这 448 份摄取样本中,有 188 份(41.9%)属于 PCa 转移灶。PET/CT检查(P<0.001)中正在进行的雄激素剥夺治疗以及SUVmax(P<0.001)和HUmean(P<0.001)的测定可独立预测骨转移。通过 10 倍内部和外部验证(n = 89 骨摄取,51% 转移;AUC,0.92),综合预测评分--骨摄取转移概率(BUMP)评分--的接受者操作特征曲线下面积(AUC)达到 0.87。BUMP 评分的 AUC 明显高于 HUmean(AUC, 0.62),并且在 HUmean 位于第一梯度的病变中保持较高水平(AUC, 0.80)。决策曲线分析表明,该评分的净获益更高。与目测评估相比,BUMP 评分在特异性方面为经验较少的 PET 阅读器提供了额外的价值(88% 对 54%,P < 0.001)。结论:在 PET 成像中出现 [18F]PSMA-1007 局灶性骨摄取的 PCa 患者中,BUMP 评分能准确区分 UBU 和骨转移,与简单评估成骨细胞 CT 相关性相比具有额外价值。它可以帮助临床医生,尤其是经验不足的临床医生解释成像结果,从而降低患者过度分期的风险。
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引用次数: 0
Clinical Factors That Influence Repeat 68Ga-PSMA-11 PET/CT Scan Positivity in Patients with Recurrent Prostate Cancer Under Observation After a Negative 68Ga-PSMA-11 PET/CT Scan: A Single-Center Retrospective Study. 影响 68Ga-PSMA-11 PET/CT 扫描阴性后接受观察的复发性前列腺癌患者重复 68Ga-PSMA-11 PET/CT 扫描阳性率的临床因素:单中心回顾性研究
Pub Date : 2024-10-01 DOI: 10.2967/jnumed.124.267591
Pan Thin, Masatoshi Hotta, Andrei Gafita, Tristan Grogan, Johannes Czernin, Jeremie Calais, Ida Sonni

This analysis aimed to identify clinical factors associated with positivity on repeat 68Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 68Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann-Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2-1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9-3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative 68Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat 68Ga-PSMA-11 PET/CT.

本分析旨在确定观察中的复发性前列腺癌(PCa)患者在扫描阴性后重复68Ga-PSMA-11 PET/CT阳性的相关临床因素。方法:这项单中心回顾性分析纳入了2016年10月至2021年6月期间在加州大学洛杉矶分校接受至少2次68Ga-PSMA-11 PET/CT扫描(PET1和PET2)的复发性PCa患者,这些患者的PET1扫描结果为阴性,且在2次扫描之间未接受PCa相关治疗。使用前列腺癌分子影像标准化评估标准来定义阴性和阳性扫描,最终队列被分为 PET2 阴性(PET2-Neg)和 PET2 阳性(PET2-Pos)。在符合纳入标准的两个以上 PET 病例中,同一 PET1 被使用两次。采用 Mann-Whitney U 检验和 Fisher exact 检验比较两组患者的特征和临床参数。计算接收者操作特征曲线下面积(AUC)和尤登指数,以确定具有统计学意义的因素的分辨能力,以及最大化灵敏度和特异性的特定切点。结果最终分析包括来自 70 名患者的 83 组 2 PET/CT 扫描。83 组中有 39 组(47%)为 PET2-阴性,83 组中有 44 组(53%)为 PET2-阳性。在所有 83 组(100%)扫描中,前列腺特异性抗原(PSA)从 PET1 增高到 PET2。PET1 时的 PSA 中位数为 0.4 纳克/毫升(四分位数间距为 0.2-1.0),PET2 时的 PSA 中位数为 1.6 纳克/毫升(四分位数间距为 0.9-3.8)。我们发现 PET2 时血清 PSA 较高(中位数,1.8 vs. 1.1 ng/mL;P = 0.015),PSA 绝对值差异(中位数,1.4 vs. 0.7 ng/mL;P = 0.006),PSA 变化百分比(中位数,+270.4% vs. +150.0%:P = 0.031)、PSA 速度中位数(0.044 vs. 0.017 ng/mL/wk,P = 0.002)和 PSA 加倍时间(DT;中位数,5.1 vs. 8.3 mo;P = 0.006),PET2-Pos 队列均短于 PET2-Neg 队列。接收器操作特征曲线显示,PET2 时 PSA 的临界值为 4.80 ng/mL(灵敏度为 34%;特异度为 92%;AUC 为 0.66),PSA 绝对值差异为 0.95 ng/mL(灵敏度为 62%;特异度为 71%;AUC 为 0.68)、PSA 阳性变化百分比为 289.50%(灵敏度为 48%;特异性为 82%;AUC 为 0.64)、PSA 速度为 0.033 纳克/毫升/周(灵敏度为 57%;特异性为 80%;AUC 为 0.70)、PSA DT 为 7.91 个月(灵敏度为 71%;特异性为 62%;AUC 为 0.67)。结论68Ga-PSMA-11 PET/CT 扫描阴性、血清 PSA 水平明显升高且 PSA DT 较短的复发性 PCa 患者在重复 68Ga-PSMA-11 PET/CT 扫描时更有可能出现阳性结果。
{"title":"Clinical Factors That Influence Repeat <sup>68</sup>Ga-PSMA-11 PET/CT Scan Positivity in Patients with Recurrent Prostate Cancer Under Observation After a Negative <sup>68</sup>Ga-PSMA-11 PET/CT Scan: A Single-Center Retrospective Study.","authors":"Pan Thin, Masatoshi Hotta, Andrei Gafita, Tristan Grogan, Johannes Czernin, Jeremie Calais, Ida Sonni","doi":"10.2967/jnumed.124.267591","DOIUrl":"10.2967/jnumed.124.267591","url":null,"abstract":"<p><p>This analysis aimed to identify clinical factors associated with positivity on repeat <sup>68</sup>Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. <b>Methods:</b> This single-center, retrospective analysis included patients who underwent at least 2 <sup>68</sup>Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann-Whitney <i>U</i> test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. <b>Results:</b> The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2-1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9-3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; <i>P</i> = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; <i>P</i> = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: <i>P</i> = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, <i>P</i> = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; <i>P</i> = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). <b>Conclusion:</b> Patients with recurrent PCa under observation after a negative <sup>68</sup>Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat <sup>68</sup>Ga-PSMA-11 PET/CT.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1571-1576"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[68Ga]Ga-PSMA-11 PET/CT-Positive Hepatic Inflammatory Pseudotumor: Possible PSMA-Avid Pitfall in Nuclear Imaging. [68Ga]Ga-PSMA-11 PET/CT 阳性肝脏炎性假瘤:核成像中可能存在的 PSMA-Avid 陷阱。
Pub Date : 2024-10-01 DOI: 10.2967/jnumed.124.267518
Fabio Monastero, Luigia Vetrone, Lina Cardisciani, Matteo Renzulli, Enrico Prosperi, Matteo Cescon, Matteo Ravaioli, Stefano Fanti, Andrea Farolfi, Francesco Vasuri
{"title":"[<sup>68</sup>Ga]Ga-PSMA-11 PET/CT-Positive Hepatic Inflammatory Pseudotumor: Possible PSMA-Avid Pitfall in Nuclear Imaging.","authors":"Fabio Monastero, Luigia Vetrone, Lina Cardisciani, Matteo Renzulli, Enrico Prosperi, Matteo Cescon, Matteo Ravaioli, Stefano Fanti, Andrea Farolfi, Francesco Vasuri","doi":"10.2967/jnumed.124.267518","DOIUrl":"10.2967/jnumed.124.267518","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1658-1659"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Navigating the Future of Prostate Cancer Care: AI-Driven Imaging and Theranostics Through the Lens of RELAINCE. 引领前列腺癌治疗的未来:从 RELAINCE 的视角看人工智能驱动的成像和治疗。
Pub Date : 2024-10-01 DOI: 10.2967/jnumed.124.267924
Aaron Jun Ning Wong, Hyun Soo Ko, Michael S Hofman
{"title":"Navigating the Future of Prostate Cancer Care: AI-Driven Imaging and Theranostics Through the Lens of RELAINCE.","authors":"Aaron Jun Ning Wong, Hyun Soo Ko, Michael S Hofman","doi":"10.2967/jnumed.124.267924","DOIUrl":"10.2967/jnumed.124.267924","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1503-1504"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluating the Utility of 18F-FDG PET/CT in Cancer of Unknown Primary. 评估 18F-FDG PET/CT 在原发性不明癌症中的实用性。
Pub Date : 2024-10-01 DOI: 10.2967/jnumed.123.267274
Tharani Sivakumaran, Anthony Cardin, Jason Callahan, Hui-Li Wong, Richard W Tothill, Rodney J Hicks, Linda R Mileshkin

Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic tumors for which standardized diagnostic work-up fails to identify the primary site. We aimed to describe the Peter MacCallum Cancer Centre experience with 18F-FDG PET/CT in extracervical CUP with respect to detection of a primary site and its impact on management. A secondary aim was to compare overall survival (OS) in patients with and without a detected primary site. Methods: CUP patients treated between 2014 and 2020 were identified from medical oncology clinics and 18F-FDG PET/CT records. Information collated from electronic medical records included the suspected primary site and treatment details before and after 18F-FDG PET/CT. Clinicopathologic details and genomic analysis were used to determine the clinically suspected primary site and compared against 2 independent masked reads of 18F-FDG PET/CT images by nuclear medicine specialists to determine sensitivity, specificity, accuracy, and the rate of detection of the primary site. Results: We identified 147 patients, 65% of whom had undergone molecular profiling. The median age at diagnosis was 61 y (range, 20-84 y), and the median follow-up time was 74 mo (range, 26-83 mo). Eighty-two percent were classified as having an unfavorable CUP subtype as per international guidelines.18F-FDG PET/CT demonstrated a primary site detection rate of 41%, resulted in a change in management in 22%, and identified previously occult disease sites in 37%. Median OS was 16.8 mo for all patients and 104.7 and 12.1 mo for favorable and unfavorable CUP subtypes, respectively (P < 0.0001). Median OS in CUP patients when using 18F-FDG PET/CT, clinicopathologic, and genomic information was 19.8 and 8.5 mo when a primary site was detected and not detected, respectively (P = 0.016). Multivariable analysis of survival adjusted for age and sex remained significant for identification of a potential primary site (P < 0.001), a favorable CUP (P < 0.001), and an Eastern Cooperative Oncology Group status of 1 or less (P < 0.001). Conclusion: 18F-FDG PET/CT plays a complementary role in CUP diagnostic work-up and was able to determine the likely primary site in 41% of cases. OS is improved with primary site identification, demonstrating the value of access to diagnostic 18F-FDG PET/CT for CUP patients.

原发部位不明的癌症(CUP)是一组异质性的转移性肿瘤,标准化的诊断检查无法确定其原发部位。我们旨在描述彼得-麦克卡勒姆癌症中心在宫颈外癌CUP中使用18F-FDG PET/CT检测原发部位的经验及其对治疗的影响。另一个目的是比较检测出原发部位和未检测出原发部位的患者的总生存率(OS)。方法从肿瘤内科诊所和 18F-FDG PET/CT 记录中确定 2014 年至 2020 年间接受治疗的 CUP 患者。从电子病历中整理的信息包括疑似原发部位以及 18F-FDG PET/CT 前后的治疗细节。临床病理详情和基因组分析用于确定临床疑似原发部位,并与核医学专家对 18F-FDG PET/CT 图像的 2 次独立遮蔽读取进行比较,以确定原发部位的敏感性、特异性、准确性和检出率。结果:我们确定了 147 名患者,其中 65% 接受了分子图谱分析。诊断时的中位年龄为 61 岁(范围为 20-84 岁),中位随访时间为 74 个月(范围为 26-83 个月)。根据国际指南,82%的患者被归类为不利CUP亚型。18F-FDG PET/CT的原发部位检出率为41%,22%的患者改变了治疗方案,37%的患者发现了之前隐匿的疾病部位。所有患者的中位生存期为 16.8 个月,CUP 亚型中位生存期分别为 104.7 个月和 12.1 个月(P < 0.0001)。使用18F-FDG PET/CT、临床病理和基因组信息时,当检测到原发部位和未检测到原发部位时,CUP患者的中位OS分别为19.8个月和8.5个月(P = 0.016)。对年龄和性别进行调整后的生存期多变量分析结果显示,潜在原发部位的确定(P < 0.001)、CUP 的良好性(P < 0.001)和东部合作肿瘤学组状态为 1 或 1 以下(P < 0.001)仍具有显著意义。结论:18F-FDG PET/CT 在 CUP 诊断工作中起辅助作用,能确定 41% 病例的可能原发部位。随着原发部位的确定,OS 有所改善,这表明了 18F-FDG PET/CT 诊断技术对 CUP 患者的价值。
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引用次数: 0
Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent 177Lu-Labeled Radiohapten. 用双价 177Lu 标记的放射噬菌体对人类结直肠癌进行 GPA33 放射免疫治疗。
Pub Date : 2024-10-01 DOI: 10.2967/jnumed.124.267685
Brett A Vaughn, Sang-Gyu Lee, Daniela Burnes Vargas, Shin Seo, Sara S Rinne, Hong Xu, Hong-Fen Guo, Alexandre B Le Roux, Leah Gajecki, Simone Krebs, Guangbin Yang, Ouathek Ouerfelli, Pat B Zanzonico, Edward K Fung, Samantha St Jean, Sebastian E Carrasco, Achim Jungbluth, Nai Kong V Cheung, Steven M Larson, Darren R Veach, Sarah M Cheal
<p><p>Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic γ- and β-emitting isotope <sup>177</sup>Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. <b>Methods:</b> Gemini was synthesized by linking 2 <i>S</i>-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [<sup>177</sup>Lu]Lu-Gemini was prepared with no-carrier-added <sup>177</sup>LuCl<sub>3</sub> to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-<sup>177</sup>Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [<sup>177</sup>Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [<sup>177</sup>Lu]Lu-<i>S</i>-2-(4-aminobenzyl)-DOTA ([<sup>177</sup>Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [<sup>177</sup>Lu]Lu-Gemini) in mouse models. <b>Results:</b> Initial in vivo studies showed that [<sup>177</sup>Lu]Lu-Gemini behaved similarly to [<sup>177</sup>Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [<sup>177</sup>Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [<sup>177</sup>Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor-to-normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [<sup>177</sup>Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [<sup>177</sup>Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [<sup>177</sup>Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [<sup>177</sup>Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). <b>Conclusion:</b> We have developed a bivalent DOTA-radiohapten, [<sup>177</sup>Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [<sup>177</sup>Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [<sup>177</sup>Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered <
放射性标记的小分子 DOTA-aptens 可与抗肿瘤/抗 DOTA 双特异性抗体(BsAbs)相结合,用于预靶向放射免疫疗法(PRIT)。为了通过基于 DOTA 的 PRIT(DOTA-PRIT)优化释放治疗性 γ 和 β 发射同位素 177Lu,我们开发了双价 Gemini(DOTA-Bn-硫脲-PEG4-硫脲-Bn-DOTA,又名(3,6,9,12-四氧杂十四烷-1,14-二基)双(DOTA-苄基硫脲))。方法:Gemini 是通过 1,14 二氨基-PEG4 连接器将 2 个 S-2-(4-异硫氰酸苄基)-DOTA 分子连接在一起而合成的。用不添加载体的 177LuCl3 制备的[177Lu]Lu-Gemini 摩尔特异性活性为 123 GBq/μmol,放射化学纯度超过 99%。体外验证了 BsAb-177Lu-Gemini 的特异性。随后,我们评估了[177Lu]Lu-Gemini 和我们的黄金标准单价[177Lu]Lu-S-2-(4-氨基苄基)-DOTA([177Lu]Lu-DOTA-Bn)在天真(无肿瘤)裸鼠体内的生物分布和全身清除率。对于我们的概念验证系统,我们在小鼠模型中使用已建立的 DOTA-PRIT 方案(抗-GPA33/抗-DOTA IgG-scFv BsAb、一种清除剂和[177Lu]Lu-Gemini)进行了三步预靶向治疗。结果:初步体内研究表明,[177Lu]Lu-Gemini的表现与[177Lu]Lu-DOTA-Bn相似,血液和全身清除动力学、生物分布和小鼠肾脏剂量测定几乎相同。将[177Lu]Lu-Gemini预靶向表达GPA33的SW1222人结直肠异种移植物非常有效,血液、肿瘤、肝脏、脾脏和肾脏的[177Lu]Lu-Gemini吸收剂量分别为3.99、455、6.93、5.36和14.0 cGy/MBq。血液和肾脏中肿瘤与正常组织的吸收剂量比(即治疗指数 [TI])分别为 114 和 33。此外,我们还证明,与单价[177Lu]Lu-DOTA-Bn相比,在DOTA-PRIT中使用二价[177Lu]Lu-Gemini可提高TIs,增强[177Lu]Lu-Gemini的肿瘤摄取和保留。最后,我们确定了 SW1222 肿瘤小鼠的疗效,证明单次注射抗 GPA33 DOTA-PRIT 和 44 MBq(1.2 mCi)[177Lu]Lu-Gemini(估计肿瘤吸收剂量为 200 Gy)可诱导 5 只动物中的 5 只出现完全反应,5 只动物中的 2 只(40%)出现组织学治愈。此外,与未接受治疗的对照组相比,存活率明显提高(未达到最大耐受剂量)。结论我们开发了一种二价 DOTA-放射性噬菌体--[177Lu]Lu-Gemini,它在 DOTA-PRIT 应用中显示出更好的放射药理学。与单价[177Lu]Lu-DOTA-Bn相比,在DOTA-PRIT中使用二价[177Lu]Lu-Gemini可以大大减少177Lu活性的用量,同时在血液(>100)和肾脏(>30)中仍能达到较高的TIs,从而实现治疗目的。
{"title":"Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent <sup>177</sup>Lu-Labeled Radiohapten.","authors":"Brett A Vaughn, Sang-Gyu Lee, Daniela Burnes Vargas, Shin Seo, Sara S Rinne, Hong Xu, Hong-Fen Guo, Alexandre B Le Roux, Leah Gajecki, Simone Krebs, Guangbin Yang, Ouathek Ouerfelli, Pat B Zanzonico, Edward K Fung, Samantha St Jean, Sebastian E Carrasco, Achim Jungbluth, Nai Kong V Cheung, Steven M Larson, Darren R Veach, Sarah M Cheal","doi":"10.2967/jnumed.124.267685","DOIUrl":"10.2967/jnumed.124.267685","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic γ- and β-emitting isotope &lt;sup&gt;177&lt;/sup&gt;Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. &lt;b&gt;Methods:&lt;/b&gt; Gemini was synthesized by linking 2 &lt;i&gt;S&lt;/i&gt;-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-Gemini was prepared with no-carrier-added &lt;sup&gt;177&lt;/sup&gt;LuCl&lt;sub&gt;3&lt;/sub&gt; to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-&lt;sup&gt;177&lt;/sup&gt;Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-&lt;i&gt;S&lt;/i&gt;-2-(4-aminobenzyl)-DOTA ([&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-Gemini) in mouse models. &lt;b&gt;Results:&lt;/b&gt; Initial in vivo studies showed that [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-Gemini behaved similarly to [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor-to-normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). &lt;b&gt;Conclusion:&lt;/b&gt; We have developed a bivalent DOTA-radiohapten, [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered &lt;","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1611-1618"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Rise of Molecular Image-Guided Robotic Surgery. 分子图像引导机器人手术的兴起。
Pub Date : 2024-10-01 DOI: 10.2967/jnumed.124.267783
Fijs W B van Leeuwen, Tessa Buckle, Matthias N van Oosterom, Daphne D D Rietbergen

Following early acceptance by urologists, the use of surgical robotic platforms is rapidly spreading to other surgical fields. This empowerment of surgical perception via robotic advances occurs in parallel to developments in intraoperative molecular imaging. Convergence of these efforts creates a logical incentive to advance the decades-old image-guided robotics paradigm. This yields new radioguided surgery strategies set to optimally exploit the symbiosis between the growing clinical translation of robotics and molecular imaging. These strategies intend to advance surgical precision by increasing dexterity and optimizing surgical decision-making. In this state-of-the-art review, topic-related developments in chemistry (tracer development) and engineering (medical device development) are discussed, and future scientific robotic growth markets for molecular imaging are presented.

继泌尿科医生早期接受机器人手术平台之后,机器人手术平台的使用正迅速扩展到其他外科领域。通过机器人提高手术感知能力的同时,术中分子成像技术也在不断发展。这些努力的汇聚为推进已有几十年历史的图像引导机器人技术范例提供了合乎逻辑的动力。这就产生了新的放射引导手术策略,旨在优化利用机器人技术和分子成像技术日益增长的临床应用之间的共生关系。这些策略旨在通过提高灵巧性和优化手术决策来提高手术精度。在这篇最新综述中,讨论了化学(示踪剂开发)和工程(医疗设备开发)领域与主题相关的发展,并介绍了分子成像科学机器人的未来增长市场。
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引用次数: 0
Challenges with 177Lu-PSMA-617 Radiopharmaceutical Therapy in Clinical Practice. 177Lu-PSMA-617 放射性药物疗法在临床实践中面临的挑战。
Pub Date : 2024-09-19 DOI: 10.2967/jnumed.124.268023
Hossein Jadvar, Amir Iravani, Lisa Bodei, Jeremie Calais
{"title":"Challenges with <sup>177</sup>Lu-PSMA-617 Radiopharmaceutical Therapy in Clinical Practice.","authors":"Hossein Jadvar, Amir Iravani, Lisa Bodei, Jeremie Calais","doi":"10.2967/jnumed.124.268023","DOIUrl":"https://doi.org/10.2967/jnumed.124.268023","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
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