Synthesis and Evaluation of 99mTc-Labeled FAP Inhibitors with Different Linkers for Imaging of Fibroblast Activation Proteins in Tumors.
J Med Chem
; 66(7): 4952-4960, 2023 04 13.
Article
em En
| MEDLINE
| ID: mdl-36972467
ABSTRACT
Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment due to its selective expression on cancer-associated fibroblasts (CAFs) in most solid tumor stroma. Two FAP inhibitor (FAPI) derived ligands (L1 and L2) containing different lengths of DPro-Gly (PG) repeat units as linkers were designed and synthesized with high affinity for FAP. Two stable hydrophilic 99mTc-labeled complexes ([99mTc]Tc-L1 and [99mTc]Tc-L2) were obtained. In vitro cellular studies show that the uptake mechanism is correlated with FAP uptake, and [99mTc]Tc-L1 shows a higher cell uptake and specific binding to FAP. A nanomolar Kd value for [99mTc]Tc-L1 indicates its significantly high target affinity for FAP. The biodistribution and microSPECT/CT images obtained for U87MG tumor mice show that [99mTc]Tc-L1 has high tumor uptake with specificity to FAP and high tumor-to-nontarget ratios. As an inexpensive, easily made, and widely available tracer, [99mTc]Tc-L1 holds great promise for clinical applications.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diagnóstico por Imagem
/
Fibroblastos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article