The tumour sink effect on ⁶⁸Ga-PSMA-PET/CT in metastatic castration-resistant prostate cancer and its implications for PSMA-RPT: a sub-analysis of the 3TMPO study.

IF 3.5 2区医学 Q2 ONCOLOGY

Cancer Imaging Pub Date : 2025-07-15 DOI:10.1186/s40644-025-00910-z

Atefeh Zamanian, Étienne Rousseau, François-Alexandre Buteau, Frédéric Arsenault, Alexis Beaulieu, Geneviève April, Daniel Juneau, Nicolas Plouznikoff, Éric E Turcotte, Catherine Allard, Patrick O Richard, Fred Saad, Brigitte Guérin, Frédéric Pouliot, Jean-Mathieu Beauregard

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引用次数: 0

Abstract

Background: The tumour sink effect is a phenomenon whereby the sequestration of a radiopharmaceutical in cancer lesions leads to decreased activity concentration in the blood stream and organs. The aim of this sub-analysis of the prospective 3TMPO study (NCT04000776) was to investigate the tumour sink effect on prostate-specific membrane antigen (PSMA) PET imaging in a population of patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: Ninety-seven participants underwent ⁶⁸Ga-PSMA-617 PET/CT imaging. The activity concentration in the kidney, parotid, spleen, liver and blood was expressed as a percentage of injected activity per cubic centimetre (%IA/cm³). The total tumour volume was delineated, and the total lesion fraction (TLF), i.e., the percentage of injected activity sequestered in the tumour, was computed. Participants were stratified into three tumour burden groups: small (TLF < 10%), moderate (10% ≤ TLF < 25%), and large (TLF ≥ 25%). Weight, lean body weight, body surface area, and estimated glomerular filtration rate (eGFR) were investigated as additional factors affecting biodistribution.

Results: The TLF ranged from 0.0 to 43.5%. For all healthy tissues, the %IA/cm³ was negatively correlated with TLF (r ranging - 0.33 to - 0.46; P < 0.001). Patients with a large TLF had significantly lower uptake in all organs when compared to those with a small TLF (P < 0.05). Body habitus indices and/or eGFR were negatively correlated with the %IA/cm³ of the parotid, liver and blood (r ranging - 0.23 to - 0.33; P < 0.05). Combining predictive variables, the term [BSA / (1-TLF)] tended to yield the strongest negative correlations with healthy tissues %IA/cm³ (r ranging - 0.33 to - 0.63; P < 0.001).

Conclusion: The tumour sink effect was observed in a cohort of mCRPC patients scanned with ⁶⁸Ga-PSMA-617. This finding strongly suggests that patients with a large TLF are likely to receive lower absorbed doses to organs at risk - i.e., be undertreated from a dosimetry perspective - following a fixed-activity regime of ¹⁷⁷Lu-PSMA-617 radiopharmaceutical therapy, as commonly practiced. Individual factors such as body habitus and renal function further impact the biodistribution of PSMA radiopharmaceuticals.

Trial registration: NCT04000776, registered on 2019-06-27.

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转移性去势抵抗性前列腺癌68Ga-PSMA-PET/CT的肿瘤沉淀效应及其对PSMA-RPT的影响：3TMPO研究的亚分析

背景：肿瘤沉淀效应是一种现象，即放射性药物在癌症病变中的隔离导致血流和器官中的活性浓度降低。这项前瞻性3TMPO研究（NCT04000776）的亚分析目的是研究肿瘤沉淀对转移性去势抵抗性前列腺癌（mCRPC）患者前列腺特异性膜抗原（PSMA） PET成像的影响。方法：97例患者行68Ga-PSMA-617 PET/CT成像。肾脏、腮腺、脾脏、肝脏和血液中的活性浓度以每立方厘米注射活性的百分比表示（%IA/cm3）。勾画出肿瘤的总体积，并计算总病变分数（TLF），即注射活性在肿瘤中被隔离的百分比。参与者被分为三个肿瘤负担组：TLF小(结果：TLF范围为0.0 - 43.5%。对于所有健康组织，%IA/cm3与TLF呈负相关(r范围为- 0.33 ~ - 0.46；腮腺、肝脏和血液的p3值(r范围为- 0.23 ~ - 0.33；p3 (r范围为- 0.33 ~ - 0.63；结论：在68Ga-PSMA-617扫描的mCRPC患者队列中观察到肿瘤吸收效应。这一发现有力地表明，TLF较大的患者可能接受较低的危险器官吸收剂量，即从剂量学的角度来看，在通常采用的177Lu-PSMA-617放射性药物治疗的固定活性方案下，治疗不足。个体因素如体质和肾功能进一步影响PSMA放射性药物的生物分布。试验注册：NCT04000776，注册日期：2019-06-27。

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来源期刊

Cancer Imaging ONCOLOGY-RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

CiteScore

7.00

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Cancer Imaging is an open access, peer-reviewed journal publishing original articles, reviews and editorials written by expert international radiologists working in oncology. The journal encompasses CT, MR, PET, ultrasound, radionuclide and multimodal imaging in all kinds of malignant tumours, plus new developments, techniques and innovations. Topics of interest include: Breast Imaging Chest Complications of treatment Ear, Nose & Throat Gastrointestinal Hepatobiliary & Pancreatic Imaging biomarkers Interventional Lymphoma Measurement of tumour response Molecular functional imaging Musculoskeletal Neuro oncology Nuclear Medicine Paediatric.