Comparative biological evaluation of [18F]fluciclovine, [18F]FBPA-Fr, and [18F]FET for boron neutron capture therapy: Preclinical validation and clinical feasibility

IF 3.1 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Nuclear medicine and biology Pub Date : 2026-05-01 Epub Date: 2026-05-20 DOI:10.1016/j.nucmedbio.2026.109636

Ting-Yu Chang , Ko-Han Lin , Tzu-Yu Lee , Yi-Ting Tsai , Yi-Wei Chen , Cheng-Lin Wu , Chun-Yi Wu

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Abstract

Purpose

The PET tracer 4‑borono-2-[¹⁸F]-fluoro-phenylalanine fructose ([¹⁸F]FBPA-Fr) is commonly used to estimate the biodistribution of L-4-dihydroxy-borylphenylalanine fructose (BPA-Fr). However, its limited regulatory approval has prompted the exploration of alternative imaging agents. In this study, we evaluated the feasibility of [¹⁸F]fluciclovine and [¹⁸F]fluoroethyl-tyrosine ([¹⁸F]FET) PET for pre-BNCT assessment, with direct comparison to [¹⁸F]FBPA-Fr.

Methods

In vitro cellular uptake studies were performed using two different cancer cell lines. In vivo microPET/MR imaging and biodistribution analyses were conducted in mice bearing wild-type and L-type amino acid transporter 1 (LAT1)-knockdown GBM8401 tumors. The therapeutic efficacy of BPA-Fr-based BNCT was evaluated in tumor-bearing mice. In addition, a pilot clinical study compared [¹⁸F]fluciclovine and [¹⁸F]FBPA-Fr PET imaging in participants with brain and head-and-neck tumors.

Results

[¹⁸F]FBPA-Fr uptake was strongly dependent on LAT1 expression, decreasing by approximately 60 % in LAT1-knockdown cells, whereas [¹⁸F]fluciclovine uptake was reduced by only ~10 %. In vivo, [¹⁸F]FET showed the highest absolute tumor uptake but the lowest tumor-to-normal brain (T/N) ratio due to high background activity. Mice with high [¹⁸F]fluciclovine tumor uptake exhibited significantly prolonged survival following BNCT (15–17 days) compared with controls (~10 days). Clinically, [¹⁸F]fluciclovine and [¹⁸F]FBPA-Fr showed comparable T/N ratios in patients with pontine glioma and maxillary sinus carcinoma. Moreover, [¹⁸F]fluciclovine PET visualized metabolic changes after BNCT, which were consistent with subsequent disease progression.

Conclusion

Although [¹⁸F]FBPA-Fr remains the most LAT1-specific tracer, [¹⁸F]fluciclovine provides comparable tumor-to-normal tissue contrast and reliable imaging performance, supporting its role as a clinically feasible alternative for pre-BNCT patient selection and treatment response assessment.

Abstract Image

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[18F]氟氯烷、[18F]FBPA-Fr和[18F]FET用于硼中子俘获治疗的比较生物学评价：临床前验证和临床可行性

目的PET示踪剂4‑硼-2-[18F]-氟苯丙氨酸果糖（[18F]FBPA-Fr）常用于估计l -4-二羟基苯丙氨酸果糖（BPA-Fr）的生物分布。然而，其有限的监管批准促使了替代显像剂的探索。在本研究中，我们评估了[18F]氟氯氟素和[18F]氟乙基酪氨酸（[18F]FET） PET用于bnct前评估的可行性，并与[18F]FBPA-Fr进行了直接比较。方法用两种不同的癌细胞系进行体外细胞摄取研究。对携带野生型和l型氨基酸转运蛋白1 （LAT1）敲低GBM8401肿瘤的小鼠进行体内pet /MR成像和生物分布分析。以bpa - fr为基础的BNCT对荷瘤小鼠的治疗效果进行了评价。此外，一项试点临床研究比较了[18F]氟氯氟素和[18F]FBPA-Fr PET在脑和头颈部肿瘤患者中的成像效果。结果[18F]FBPA-Fr的摄取强烈依赖于LAT1的表达，在LAT1敲除的细胞中，FBPA-Fr的摄取减少了约60%，而[18F]氟氯草的摄取仅减少了约10%。在体内，[18F]FET显示出最高的绝对肿瘤摄取，但由于高背景活性，肿瘤与正常脑（T/N）比最低。与对照组（~10天）相比，高[18F]氟氯叶肿瘤摄取的小鼠在BNCT后的存活时间明显延长（15-17天）。在临床上，[18F]氟氯梵与[18F]FBPA-Fr在脑桥胶质瘤和上颌窦癌患者中的T/N比值相当。此外，[18F]氟氯叶PET显示BNCT后的代谢变化，这与随后的疾病进展一致。尽管[18F]FBPA-Fr仍然是最具lat1特异性的示踪剂，但[18F]氟氯叶碱提供了与正常肿瘤相当的组织对比和可靠的成像表现，支持其作为bnct前患者选择和治疗反应评估的临床可行替代方案。

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

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.