H3RESCA chelator-enabled [18F]AlF labeling: An optimized temperature-resilient platform for PSMA-targeted PET tracers in prostate cancer

IF 3 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Nuclear medicine and biology Pub Date : 2026-03-01 Epub Date: 2026-01-22 DOI:10.1016/j.nucmedbio.2026.109603

Yukai Zhang , Zhoumi Hu , Qingyu Zhang , Bowu Zhang , Jingye Li , Jianjun Liu , Cheng Wang

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引用次数: 0

Abstract

Objective: Prostate-specific membrane antigen (PSMA) has emerged as a pivotal biomarker for the molecular imaging and targeted therapy of prostate cancer. To address the ongoing need for PSMA-targeting radiotracers with improved mild-labeling capability and reduced non-target organ exposure, beyond currently approved agents (e.g., [⁶⁸Ga]Ga-PSMA-11) that require higher temperatures or show hepatobiliary clearance, a novel ¹⁸F-labeled PSMA inhibitor, [¹⁸F]AlF-H₃RESCA-PSMA, was developed for PET imaging of prostate cancer.

Methods

H₃RESCA-PSMA was synthesized with an acyclic pentadentate chelator and radiolabeled with [¹⁸F]AlF at room temperature. Biodistribution and PET/CT studies were performed in PSMA-positive tumor xenografts, with [¹⁸F]AlF-PSMA-RESCA1 as comparator.

Results

Radiochemical yield was 75.5 ± 5.0%. [¹⁸F]AlF-H₃RESCA-PSMA showed 2-fold higher tumor uptake and slower wash-out versus PSMA-RESCA1, while exhibiting markedly reduced liver and kidney retention. PET images revealed superior tumor contrast and faster background clearance.

Conclusions

[¹⁸F]AlF-H₃RESCA-PSMA offers enhanced PSMA-targeting specificity and imaging contrast, supporting its clinical translation for prostate cancer PET.

Abstract Image

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H3RESCA螯合剂激活的AlF标记：psma靶向PET示踪剂在前列腺癌中的温度弹性优化平台

目的：前列腺特异性膜抗原（PSMA）已成为前列腺癌分子成像和靶向治疗的关键生物标志物。除了目前已批准的需要更高温度或显示肝胆清除率的药物（如[68Ga]Ga-PSMA-11）外，为了满足对PSMA靶向放射性示踪剂的持续需求，研究人员开发了一种新型18F标记的PSMA抑制剂[18F]AlF-H3RESCA-PSMA，用于前列腺癌的PET成像。方法采用无环五齿酸螯合剂合成sh3resca - psma，并在室温下用[18F]AlF进行放射性标记。以[18F]AlF-PSMA-RESCA1为比较物，对psma阳性肿瘤异种移植物进行生物分布和PET/CT研究。结果放射化学产率为75.5±5.0%。[18F]与PSMA-RESCA1相比，half - h3resca - psma的肿瘤摄取率高2倍，洗脱速度较慢，同时肝脏和肾脏潴留明显减少。PET图像显示较好的肿瘤对比和较快的背景清除。结论[18F]AlF-H3RESCA-PSMA具有增强的psma靶向特异性和成像对比度，支持其在前列腺癌PET中的临床应用。

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来源期刊

Nuclear medicine and biology 医学-核医学

CiteScore

6.00

自引率

9.70%

发文量

479

审稿时长

51 days

期刊介绍： Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized. These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field. Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.