Rational Design, Pharmacomodulation, and Synthesis of [68Ga]Ga-Alb-FAPtp-01, a Selective Tumor-Associated Fibroblast Activation Protein Tracer for PET Imaging of Glioma.

Dynamic changes in the tumor-associated fibroblast activation protein (FAP) expression in tumors of different stages may be helpful for prognostic evaluation and treatment response monitoring, making this protein a promising surveillance biomarker for timely diagnosis of malignant tumors and effective planning of patient care. To prospectively verify the diagnostic efficacy value of the developed FAP tracers, [68Ga]Ga-FAPtp and [68Ga]Ga-Alb-FAPtp-01, dynamic/static positron emission tomography (PET)/computed tomography scans were acquired for tumor-targeting studies in vivo and in comparison with the well-established clinically used tracer [68Ga]Ga-FAPI-04. The optimized rationally designed FAP-targeting PET tracer, [68Ga]Ga-Alb-FAPtp-01, with albumin-binding capability demonstrated prominent tumor uptake over time. The mean standard uptake value (SUV) and the tumor/muscle (T/M) ratio were as high as 1.775 ± 0.179 SUV and T/M = 5.9, 1.533 ± 0.222 SUV and T/M = 6.7, and 1.425 ± 0.204 SUV and T/M = 9.5, respectively, at 1, 2, and 3 h. Its improved tumor uptake and pharmacokinetics suggest that the [68Ga]Ga-Alb-FAPtp-01 tracer can noninvasively detect FAP activation in vivo, permitting a precise definition of its roles in tumors of different stages and yielding insights regarding FAP-targeted radiotherapeutic strategies at the molecular level.