A comparison of [ 18 F]AlF- and 68 Ga-labeled dual targeting heterodimer FAPI-RGD in malignant tumor: preclinical evaluation and pilot clinical PET/CT imaging

Due to the heterogeneity of tumors, strategies to improve the effectiveness of dual-targeting tracers in tumor diagnostics have been intensively practiced. In this study, the radiolabeled [ 18 F]AlF-NOTA-FAPI-RGD (denoted as [ 18 F]AlF-LNC1007), a dual-targeting heterodimer tracer targeting both fibroblast activation protein (FAP) and integrin α v β 3 to enhance specific tumor uptake and retention, was synthesized and evaluated. The tracer was compared with [ 68 Ga]Ga-LNC1007 in preclinical and clinical settings. Methods The preparation of [ 18 F]AlF- and 68 Ga-labeled FAPI-RGD was carried out with an optimized protocol. The stability was tested in PBS and fetal bovine serum (FBS). Cellular uptake and in vivo distribution of the two products were compared and carried out on the U87MG cell line and its xenograft model. The safety and dosimetry of [ 18 F]AlF-LNC1007 PET/CT scan were evaluated in six patients with malignant tumors. Results Two radiolabeling protocols of [ 18 F]AlF-/[ 68 Ga]Ga-LNC1007 were developed and optimized to give a high yield of tracers with good stability. In vivo microPET images showed that the two tracers exhibited comparable pharmacokinetic characteristics, with high tumor uptake and prolonged tumor retention. In vivo distribution data showed that the target-to-non-target ratios of [ 18 F]AlF-LNC1007 were similar to[ 68 Ga]Ga-LNC1007. A total of six patients underwent [ 18 F]AlF-LNC1007 PET/CT evaluation while two had head-to-head [ 18 F]FDG PET/CT scans. The total body effective dose was 9.94E-03 mSv/MBq. The biodistribution curve showed optimal normal organ uptake with high tumor uptake and long retention of up to 3h p.i., and notably, the tumor-to-background ratio increased over time. Conclusion We successfully prepared an [ 18 F]AlF-LNC1007 dual-targeting PET probe with comparable performances as [ 68 Ga]Ga-LNC1007. With prolonged tumor retention and tumor specificity, it produced good imaging quality in preclinical and clinical translational studies, indicating that [ 18 F]AlF-LNC1007 is a promising non-invasive tracer for detecting tumors expressing FAP and/or integrin a v β 3 , with the prospect of clinical implementation.