作为 HER2 肿瘤成像的新型分子探针,[18F]AlF-RESCA-5F7 的放射合成和临床前评估。

IF 2 Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
American journal of nuclear medicine and molecular imaging Pub Date : 2024-06-15 eCollection Date: 2024-01-01 DOI:10.62347/BVPK1360
Ruhua Tian, Jinping Kong, Yingfang He, Guoqiang Xu, Tengxiang Chen, Junbin Han
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引用次数: 0

摘要

HER2 过表达与多种肿瘤类型有关,促使人们开发靶向疗法。此前,异[211At]SGMAB-5F7 被开发为 HER2 靶向α治疗药物,在临床前阶段显示出良好的疗效。为了寻找一种 18F 标记的示踪剂用于临床转化中的辅助诊断,我们在目前的工作中采用了 Al18F-RESCA 策略,并研究了[18F]AlF-RESCA-5F7 是否能在体内观察到 HER2 的表达。[18F]AlF-RESCA-5F7的放射化学纯度很高(> 99%),摩尔活性在16.5 ± 8.8 GBq/μmol(n = 8)之间。与之前报道的含有 5F7 作为 HER2 靶向载体和氟-18 作为正电子发射同位素的放射性racers 相比,该放射性合成简化为 30 分钟内的一个步骤。通过使用 SKOV3 卵巢癌细胞进行饱和结合试验,确定[18F]AlF-RESCA-5F7 的解离常数为 3.3 nM。注射后 1、2 和 4 h,SKOV3 异种移植的 Balb/c 裸鼠对这种新型示踪剂的肿瘤摄取率分别为 4.69 ± 1.51、3.34 ± 0.82 和 3.77 ± 0.99 %ID/g。尽管肾脏的放射性保留率很高,但[18F]AlF-RESCA-5F7的显微PET/CT成像可在注射后4小时内描绘出肿瘤的轮廓,而胆囊、肠道和骨骼的放射性活性极低。这项研究表明,[18F]AlF-RESCA-5F7 是一种很有前途的 HER2 PET 放射性示踪剂,其放射性标记方法简单易行。至于[18F]AlF-RESCA-5F7能否作为辅助诊断药物,协助患者分层和监测异[211At]SGMAB-5F7的治疗情况,还有待进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Radiosynthesis and preclinical evaluations of [18F]AlF-RESCA-5F7 as a novel molecular probe for HER2 tumor imaging.

HER2 overexpression is associated with various tumor types and prompted the development of targeted therapies. Previously, iso-[211At]SGMAB-5F7 was developed as a HER2-targeted alpha therapy agent, demonstrating promising therapeutic efficacy in the preclinical stage. Aiming for an 18F-labeled tracer for companion diagnostics in clinical translation, we employed the Al18F-RESCA strategy in our current work and investigated whether [18F]AlF-RESCA-5F7 could visualize HER2 expression in vivo. [18F]AlF-RESCA-5F7 was attained with high radiochemical purity (> 99%) and molar activity in the range of 16.5 ± 8.8 GBq/μmol (n = 8). Compared to previously reported radiotracers that contained 5F7 as the HER2-targeting carrier and fluorine-18 as the positron-emitting isotope, the radiosynthesis was simplified to one single step within 30 min. The dissociation constant of [18F]AlF-RESCA-5F7 was determined as 3.3 nM via saturation binding assay using SKOV3 ovarian carcinoma cells. Tumor uptake of the novel tracer in Balb/c nude mice bearing SKOV3 xenografts was 4.69 ± 1.51, 3.34 ± 0.82 and 3.77 ± 0.99 %ID/g at 1, 2, and 4 h post-injection. Even though high retention of radioactivity was seen in the kidneys, micro-PET/CT imaging of [18F]AlF-RESCA-5F7 delineated the tumor up to 4 h post-injection with minimal activity in the gallbladder, intestines, and bone. This study suggests that [18F]AlF-RESCA-5F7 is a promising HER2 PET radiotracer with an eased radiolabeling method. Whether [18F]AlF-RESCA-5F7 could work as a companion diagnostic agent to assist in patient stratification and treatment monitoring of iso-[211At]SGMAB-5F7 warrants further investigation.

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来源期刊
American journal of nuclear medicine and molecular imaging
American journal of nuclear medicine and molecular imaging RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING-
自引率
4.00%
发文量
4
期刊介绍: The scope of AJNMMI encompasses all areas of molecular imaging, including but not limited to: positron emission tomography (PET), single-photon emission computed tomography (SPECT), molecular magnetic resonance imaging, magnetic resonance spectroscopy, optical bioluminescence, optical fluorescence, targeted ultrasound, photoacoustic imaging, etc. AJNMMI welcomes original and review articles on both clinical investigation and preclinical research. Occasionally, special topic issues, short communications, editorials, and invited perspectives will also be published. Manuscripts, including figures and tables, must be original and not under consideration by another journal.
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