Abstract
BackgroundFibroblast activating protein (FAP) has become an important target for cancer diagnostic imaging and targeted radiotherapy. In particular, [18F]FAPI-42 has been successfully applied to positron emission tomography (PET) imaging of various tumors. However, it exhibits high hepatobiliary metabolism and is thus not conducive to abdominal tumor imaging. This study reports a novel 18F-labeled FAP inhibitor, [18F]AlF-FAPT, a better FAPI imaging agent than [18F]FAPI-42.Materials and MethodsThe precursor of [18F]AlF-FAPT (NOTA-FAPT) was designed and synthesized using the standard FMOC solid phase synthesis method. [18F]AlF-FAPT was subsequently synthesized and radiolabeled with 18F using the AllInOne synthesis module. Dynamic MicroPET and biodistribution studies of [18F]AlF-FAPT were then conducted in xenograft tumor mouse models to determine its suitability.ResultsThe precursors NOTA-FAPT were obtained with a chemical purity of > 95%. [18F]AlF-FAPT was synthesized automatically using the cassette-based module AllInOne within 40 min. The non-decay corrected radiochemical yield was 25.0 ± 5.3% (n=3). In vivo imaging and biodistribution studies further demonstrated that compared with [18F]-FAPI-42, [18F]AlF-FAPT had a lower hepatobiliary uptake than [18F]FAPI-42, which was advantageous for imaging abdominal tumors.Conclusion[18F]AlF-FAPT can be synthesized automatically using a one-step method of aluminum fluoride. Collectively, [18F]AlF-FAPT is a better FAPI imaging agent than [18F]FAPI-42. This study proves the feasibility of using [18F]AlF-FAPT as a new radioactive tracer for PET imaging.
Highlights
Traditional cancer diagnosis and treatment methods mainly targeted the tumor parenchyma cells
The precursors and reference compounds of [19F] AlF-FAPT identified by high-resolution mass spectrometry (HRMS) had a chemical purity of > 95% (Figure 3A; Supplementary Figures S1–S3, and Table S1)
The appearance of [18F]AlF-FAPT products had a colorless appearance free from particles, with a half-life of between 105 and 115 min. Both aerobes and anaerobes were negative after dilution of the product, with the bacterial endotoxin per 1mL being less than 15 EU and the ethanol content less than 5% (Table 2)
Summary
Traditional cancer diagnosis and treatment methods mainly targeted the tumor parenchyma cells. FAP has dipeptidyl peptidase and collagenase activity, which can cleave many dipeptidyl peptidase activity substrates such as gelatin and denatured type I collagen in the matrix and participate in the degradation of extracellular matrix (ECM). It promotes tumor cell detachment, invasion, and metastasis from the primary site [5, 6]. Though it is almost nonexistent in normal tissues, it is highly expressed in cancer-associated fibroblasts (CAF) of various tumors, such as ovarian, pancreatic, and hepatocellular carcinoma [7]. [18F]FAPI-42 has been successfully applied to positron emission tomography (PET) imaging of various tumors. Dynamic MicroPET and biodistribution studies of [18F]AlF-FAPT were conducted in xenograft tumor mouse models to determine its suitability
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