Clinical translational evaluation of Al18F-NOTA-FAPI for fibroblast activation protein-targeted tumour imaging

Abstract

In this study, a novel Al 18 F-NOTA-FAPI probe was developed for fibroblast activation protein (FAP) targeted tumour imaging, which was available to achieve curie level radioactivity by automatic synthesizer. The tumour detection efficacy of Al 18 F-NOTA-FAPI was further validated both in preclinical and clinical translational studies. MethodsThe radiolabeling procedure of Al 18 F-NOTA-FAPI was optimized. Cell uptake and competitive binding assay were completed with U87MG and A549 cell lines, to evaluate the affinity and specificity of Al 18 F-NOTA-FAPI probe. The biodistribution, pharmacokinetics, radiation dosimetry and tumour imaging efficacy of Al 18 F-NOTA-FAPI probe were researched with healthy Kunming (KM) and/or U87MG model mice.After the approval of ethical committee, Al 18 F-NOTA-FAPI probe was translated into clinical for the PET/CT imaging of first 10 cancer patients. ResultsThe radiolabeling yield of Al 18 F-NOTA-FAPI was 33.8 ± 3.2% through manually operation (n = 10), with the radiochemical purity over than 99% and the specific activity of 9.3-55.5 MBq/nmol. Whole body effective dose of Al 18 F-NOTA-FAPI was estimated to be 1.24E-02 mSv/MBq, lower than several other FAPI probes ( 68 Ga-FAPI-04, 68 Ga-FAPI-46 and 68 Ga-FAPI-74). In U87MG tumour bearing mice, Al 18 F-NOTA-FAPI showed good tumor detection efficacy from the results of micro PET/CT imaging and biodistribution studies. In organ biodistribution study of human patients, Al 18 F-NOTA-FAPI showed lower SUVmean than 2-[ 18 F]FDG in most organs, especially in 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, Al 18 F-NOTA-FAPI do not show extensive bone uptakes, and was able to find out more tumour lesions than 2-[ 18 F]FDG in the PET/CT imaging of several patients. ConclusionAl 18 F-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 human cancer patients.

A Prospective Comparison of [18F]FAPI-42 and [68Ga]Ga-FAPI-04 PET/CT in Patients With Various Cancers

“…In the present study, we selected various tumors for [ 18 F]FAPI-42 scanning, including [ 18 F]FDG avid tumors, such as lung cancer, colorectal cancer and sarcoma, and some tumors prone to be [ 18 F]FDG nonavid, such as gastric cancer and hepatocellular cancer [32]. Our data indicated that all lesions were positive on [ 18 F]FAPI-42 scan, which implied that [ 18 F]FAPI-42 may play a supplementary role to [ 18 F]FDG, similar to recently reported of [ 68 Ga]Ga-FAPI-04 [20]. When compared with [ 68 Ga]Ga-FAPI-04, our results…”

“…[ 18 F]FAPI-42 accumulation in bone was low on PET/CT image in all patients, which indicated that no de uorination occurred in vivo. Of note, [ 18 F]FAPI-42 showed high bone uptake in preclinical mice models, as reported in our previous work and in the literature [20].…”

“…Ga-labeled FAP probes have recently been proven useful for the detection of tumors with high expression of FAP and can be used for imaging various cancers [12,[26][27][28]. To take advantage of the favorable properties of uorine-18, a few 18 F-labeled FAPI probes have been introduced for PET imaging [20,21,27,29]. However, clinical data comparing 68 Ga-labeled and 18 F-labeled FAP tracers are scarce and the suitable time for the detection of tumors also needs to be identi ed for 18 The optimal image acquisition time for [ 18 F]FAPI-42 was determined to be 1 hour p.i.…”

“…The reaction mixture was heated at 100 ºC for 10 min and puri ed by simple solid-phase extraction of the product by cartridge separation. Analysis and quality control of the prepared products were performed as previously reported [11,12,20].…”

“…18 F-labeled radiopharmaceuticals have a longer half-life (T 1/2 = 109.8 min) and can thus be delivered over longer distances. Furthermore, the low positron energy of ]FAPI-42 had a good performance for depicting malignant tumors [20]. However, it is not precisely clear whether [ 18 F]FAPI-42 performs as well as [ 68 Ga]Ga-FAPI-04 in the detection of tumors.…”