Preclinical study and first-in-human imaging of [18F]FAP-2286, and comparison with 2-[18F]FDG PET/CT in various cancer patients.
Eur J Nucl Med Mol Imaging
; 51(7): 2012-2022, 2024 Jun.
Article
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| MEDLINE
| ID: mdl-38326656
ABSTRACT
PURPOSE:
Fibroblast-activated protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) of many solid cancers, but low or absent in normal tissues. Our study aimed to develop a novel FAP-specific tracer, namely [18F]FAP-2286, and evaluated its performance in comparison with well-established agents such as [18F]FAPI-42 and [68Ga]Ga-FAP-2286 in preclinical research, as well as 2-[18F]FDG in pilot clinical study.METHODS:
[18F]FAP-2286 was manually synthesized in accordance with Good Manufacturing Practice (GMP). Subsequent investigations encompassed cell uptake, competitive binding affinity, internalization and efflux assays using HT-1080hFAP cell lines. PET imaging and biodistribution studies were conducted in HEK-293ThFAP, A549hFAP, HT-1080hFAP tumor-bearing mice as well as HEK-293T, A549 and HT-1080 control groups. Furthermore, clinical evaluation of [18F]FAP-2286 was performed in fifteen patients with various cancers compared to 2-[18F]FDG PET.RESULTS:
The radiolabeling yield of [18F]FAP-2286 was 30.53 ± 5.20%, with a radiochemical purity exceeding 97%. In cell assays, [18F]FAP-2286 showed specific uptake, high internalization fraction and low cellular efflux. Rapid tumor uptake and satisfactory tumor retention was observed on micro-PET imaging and cancer patients. Meanwhile, the clinical research demonstrated that [18F]FAP-2286 may represent an alternative for low glucose-metabolism malignant tumors PET imaging such as gastric cancers.CONCLUSION:
[18F]FAP-2286 showed superior imaging quality including rapid and high target uptake and satisfactory retention in both tumor-bearing mice and cancer patients. It may emerge as a promising candidate for early or delayed phase imaging and 2-[18F]FDG non-avid cancers PET scan.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fluorodesoxiglucosa F18
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Tomografía Computarizada por Tomografía de Emisión de Positrones
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Neoplasias
Límite:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Nucl Med Mol Imaging
Asunto de la revista:
MEDICINA NUCLEAR
Año:
2024
Tipo del documento:
Article
País de afiliación:
China