FAPI-04

To evaluate the radioactive distribution patterns of [ 68 Ga]Ga-FAPI-04 in primary hepatocellular carcinoma (HCC).

Twenty-three primary HCC patients (26 lesions) from a prospective trial (ChiCTR2000039099) underwent both [ 18 F]FDG and [ 68 Ga]Ga-FAPI-04 PET/CT within 1 week. Uptake at tumor margins versus centers was compared.

FAPI-04 uptake was significantly higher at tumor margins than centers (SUVmax, P <0.001; SUVmean, P <0.01). As SUVmax thresholds increased, FAPI volume of interest concentrated at the margins and decreased sharply in the centers.

[ 68 Ga]Ga-FAPI-04 PET/CT demonstrated higher marginal uptake and pronounced central heterogeneity (low-SUV centers) in HCC. Strong peripheral uptake supports the use of FAP-targeted fluorescence-guided surgery and targeted treatment of marginal residual/recurrent disease, while low central uptake may limit FAP-targeted therapy.

Fibroblast activation protein (FAP), which is overexpressed in malignant epithelial tumors, represents a key therapeutic and diagnostic target. This study reports the development and evaluation of a novel FAP-targeted SPECT radiotracer, [^99mTc]4. The precursor was synthesized and labeled with ^99mTc using a one-pot labeling procedure, yielding a radiochemical purity exceeding 95%. The tracer exhibited high hydrophilicity (log P = -1.366 ± 0.004) and demonstrated excellent stability in PBS and serum over 7 h. In vitro, [^99mTc]4 showed specific uptake and rapid internalization in FAP-positive cells, which could be effectively blocked by competitive FAP inhibitors. In vivo SPECT/CT imaging and biodistribution studies in U87MG tumor-bearing mice revealed modest and specific tumor uptake, which was significantly reduced by co-injection with FAPI-04, confirming FAP-mediated targeting. These findings indicate that [^99mTc]4 is a highly promising candidate for noninvasive SPECT imaging of FAP expression in tumors, providing a valuable tool for tumor diagnosis and therapeutic monitoring.