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两位专家和一位新手：[F]PARPi 与 [F]FTT 与 [F]FPyPARP——PARP 成像剂的比较。

Two experts and a newbie: [F]PARPi vs [F]FTT vs [F]FPyPARP-a comparison of PARP imaging agents.

机构信息

Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Roentgenweg 15, 72076, Tuebingen, Germany.

Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University Tuebingen, Tuebingen, Germany.

出版信息

Eur J Nucl Med Mol Imaging. 2022 Feb;49(3):834-846. doi: 10.1007/s00259-021-05436-7. Epub 2021 Sep 6.

DOI:10.1007/s00259-021-05436-7
PMID:34486071
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8803746/
Abstract

PURPOSE

Imaging of PARP expression has emerged as valuable strategy for prediction of tumor malignancy. While [F]PARPi and [F]FTT are already in clinical translation, both suffer from mainly hepatobiliary clearance hampering their use for detection of abdominal lesions, e.g., liver metastases. Our novel radiotracer [F]FPyPARP aims to bridge this gap with a higher renal clearance and an easily translatable synthesis route for potential clinical application.

METHODS

We developed a less lipophilic variant of [F]PARPi by exchange of the fluorobenzoyl residue with a fluoronicotinoyl group and automated the radiosyntheses of the three radiotracers. We then conducted a comparative side-by-side study of [F]PARPi, [F]FPyPARP, and [F]FTT in NOD.CB17-Prkdc/J mice bearing HCC1937 xenografts to assess xenograft uptake and pharmacokinetics focusing on excretion pathways.

RESULTS

Together with decent uptake of all three radiotracers in the xenografts (tumor-to-blood ratios 3.41 ± 0.83, 3.99 ± 0.99, and 2.46 ± 0.35, respectively, for [F]PARPi, [F]FPyPARP, and [F]FTT), a partial shift from hepatobiliary to renal clearance of [F]FPyPARP was observed, whereas [F]PARPi and [F]FTT show almost exclusive hepatobiliary clearance.

CONCLUSION

These findings imply that [F]FPyPARP is an alternative to [F]PARPi and [F]FTT for PET imaging of PARP enzymes.

摘要

目的

PARP 表达的成像已成为预测肿瘤恶性程度的有价值策略。虽然 [F]PARPi 和 [F]FTT 已经在临床转化中，但两者都主要通过肝胆清除，这阻碍了它们在检测腹部病变（例如肝转移）中的应用。我们的新型放射性示踪剂 [F]FPyPARP 旨在通过更高的肾清除率和易于转化的合成途径来弥补这一差距，从而为潜在的临床应用提供可能性。

方法

我们通过用氟代烟酰基取代氟苯甲酰基来开发 [F]PARPi 的疏脂性较低的变体，并自动化了三种放射性示踪剂的放射合成。然后，我们在荷 HCC1937 异种移植瘤的 NOD.CB17-Prkdc/J 小鼠中进行了 [F]PARPi、[F]FPyPARP 和 [F]FTT 的并排比较研究，以评估外植体摄取和药代动力学，重点关注排泄途径。

结果

所有三种放射性示踪剂在异种移植瘤中的摄取都相当可观（肿瘤与血液的比值分别为 3.41±0.83、3.99±0.99 和 2.46±0.35，分别为 [F]PARPi、[F]FPyPARP 和 [F]FTT），[F]FPyPARP 的清除途径从肝胆向肾部分转移，而 [F]PARPi 和 [F]FTT 则显示出几乎完全的肝胆清除。

结论

这些发现表明，[F]FPyPARP 是 [F]PARPi 和 [F]FTT 用于 PARP 酶 PET 成像的替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0058/8803746/4162530b6df1/259_2021_5436_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0058/8803746/ee98eee0c705/259_2021_5436_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0058/8803746/a6157729d6d2/259_2021_5436_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0058/8803746/4162530b6df1/259_2021_5436_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0058/8803746/ee98eee0c705/259_2021_5436_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0058/8803746/a6157729d6d2/259_2021_5436_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0058/8803746/4162530b6df1/259_2021_5436_Fig3_HTML.jpg

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