Clinical translational evaluation of Al18F-NOTA-FAPI for fibroblast activation protein-targeted tumour imaging.
Eur J Nucl Med Mol Imaging
; 48(13): 4259-4271, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34165601
PURPOSE: In this study, a novel aluminium-[18F]fluoride (Al18F)-labelled 1,4,7triazacyclononane-N,N',Nâ³-triacetic acid (NOTA)-conjugated fibroblast activation protein inhibitor (FAPI) probe, named Al18F-NOTA-FAPI, was developed for fibroblast activation protein (FAP)-targeted tumour imaging; it could deliver hundreds of millicuries of radioactivity using automated synthesis. The tumour detection efficacy of Al18F-NOTA-FAPI was further validated in both preclinical and clinical translational studies. METHODS: The radiolabelling procedure of Al18F-NOTA-FAPI was optimized. Cell uptake and competitive binding assays were completed with the U87MG and A549 cell lines to evaluate the affinity and specificity of the Al18F-NOTA-FAPI probe. The biodistribution, pharmacokinetics, radiation dosimetry and tumour imaging efficacy of the Al18F-NOTA-FAPI probe were researched in healthy Kunming (KM) and/or U87MG model mice. After the approval of the ethical committee, the Al18F-NOTA-FAPI probe was translated into the clinic for PET/CT imaging of the first 10 cancer patients. RESULTS: The radiolabelling yield of Al18F-NOTA-FAPI was 33.8 ± 3.2% using manual synthesis (n = 10), with a radiochemical purity over 99% and the specific activity of 9.3-55.5 MBq/nmol. The whole body effective dose of Al18F-NOTA-FAPI was estimated to be 1.24E - 02 mSv/MBq, which was lower than several other FAPI probes (68Ga-FAPI-04, 68Ga-FAPI-46 and 68Ga-FAPI-74). In U87MG tumour-bearing mice, Al18F-NOTA-FAPI showed good tumour detection efficacy based on the results of micro PET/CT imaging and biodistribution studies. In an organ biodistribution study of patients, Al18F-NOTA-FAPI showed a lower SUVmean than 2-[18F]-fluoro-2-deoxy-D-glucose (2-[18F]FDG) in most organs, especially in the liver (1.1 ± 0.2 vs. 2.0 ± 0.9), brain (0.1 ± 0.0 vs. 5.9 ± 1.3), and bone marrow (0.9 ± 0.1 vs. 1.7 ± 0.4). Meanwhile, Al18F-NOTA-FAPI did not show extensive bone uptake, and was able to detect more lesions than 2-[18F]FDG in the PET/CT imaging of several patients. CONCLUSION: The Al18F-NOTA-FAPI probe was successfully fabricated and applied in fibroblast activation protein-targeted tumour PET/CT imaging, which showed excellent imaging quality and tumour detection efficacy in U87MG tumour-bearing mice as well as in cancer patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000038080. Registered 09 September 2020. http://www.chictr.org.cn/showproj.aspx?proj=61192.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
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Neoplasias
Tipo de estudo:
Guideline
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article