All that glitters is not gold: high uptake on PSMA PET in non-prostate cancers does not mean that treatment with [¹⁷⁷Lu]Lu-PSMA-radioligand will be successful.

IF 3.1 3区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

EJNMMI Research Pub Date : 2024-10-15 DOI:10.1186/s13550-024-01156-9

Trond Velde Bogsrud, Ola Engelsen, Thuy Thu Thi Lu, Andreas Stensvold, Derek R Johnson, Brian J Burkett, Ayse Tuba Kendi, Mukesh K Pandey, Rune Sundset, Jolanta M Durski

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引用次数: 0

Abstract

Background: The main objective is to discuss why treatment of non-prostate cancers with [¹⁷⁷Lu]Lu-PSMA-radioligand achieved only low tumor dose in most published cases, despite high uptake on PSMA PET. We use a patient with renal cell carcinoma as an illustrative example. Furthermore, we discuss how the problem with early washout and low tumor dose might be overcome by using a radionuclide with shorter half-life, matching the target binding residence time.

Case presentation: [⁶⁸Ga]Ga-PSMA-11 PET/CT of a 56-year old man with metastatic renal cell carcinoma showed high lesion uptake. One dose of 6.9 GBq [¹⁷⁷Lu]Lu-PSMA-I&T was administrated. Post-therapy dosimetry was performed with SPECT/CT and whole-body planar imaging after 5, 24 and 48 h. Doses to target lesions were only 0.2-0.5 Gy. No treatment effect was achieved.

Conclusion: Rapid tumor washout of [¹⁷⁷Lu]Lu-PSMA-I&T and low tumor dose despite high uptake of [⁶⁸Ga]Ga-PSMA-11 are most likely caused by localization of PSMA-receptors on neovasculature rather than on the tumor cells, and unlike in prostate cancer cells, the PSMA-RL / PSMA-receptor complex is not internalized. To overcome the problem with early washout, the use of a radionuclide with shorter half-life matching the target binding residence time will be needed.

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金无足赤：非前列腺癌 PSMA PET 的高摄取率并不意味着[177Lu]Lu-PSMA-放射性配体的治疗一定会成功。

背景：主要目的是讨论为什么用[177Lu]Lu-PSMA-放射性配体治疗非前列腺癌时，尽管PSMA PET摄取量很高，但在大多数已发表的病例中，肿瘤剂量却很低。我们以一名肾细胞癌患者为例进行说明。此外，我们还讨论了如何通过使用半衰期较短的放射性核素来克服早期冲刷和低肿瘤剂量的问题，使之与靶点结合停留时间相匹配：病例介绍：[68Ga]Ga-PSMA-11 PET/CT显示，一名患有转移性肾细胞癌的56岁男子的病灶摄取量很高。患者接受了一剂 6.9 GBq [177Lu]Lu-PSMA-I&T 的治疗。5、24和48小时后，通过SPECT/CT和全身平面成像进行了治疗后剂量测定。没有达到治疗效果：结论：[177Lu]Lu-PSMA-I&T的快速肿瘤冲洗和[68Ga]Ga-PSMA-11的高摄取但低肿瘤剂量很可能是由于PSMA-受体定位于新生血管而非肿瘤细胞，而且与前列腺癌细胞不同，PSMA-RL/PSMA-受体复合物没有被内化。为了克服早期冲洗的问题，需要使用半衰期较短的放射性核素，使其与目标结合停留时间相匹配。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EJNMMI Research RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING&nb-

CiteScore

5.90

自引率

3.10%

发文量

审稿时长

13 weeks

期刊介绍： EJNMMI Research publishes new basic, translational and clinical research in the field of nuclear medicine and molecular imaging. Regular features include original research articles, rapid communication of preliminary data on innovative research, interesting case reports, editorials, and letters to the editor. Educational articles on basic sciences, fundamental aspects and controversy related to pre-clinical and clinical research or ethical aspects of research are also welcome. Timely reviews provide updates on current applications, issues in imaging research and translational aspects of nuclear medicine and molecular imaging technologies. The main emphasis is placed on the development of targeted imaging with radiopharmaceuticals within the broader context of molecular probes to enhance understanding and characterisation of the complex biological processes underlying disease and to develop, test and guide new treatment modalities, including radionuclide therapy.