Synthesis, preclinical evaluation and clinical application of a novel heterodimeric tracer ⁶⁸Ga-pentixafor-c(RGDfK)...

CXCR4 and integrin α_vβ₃ play important roles in tumor biology and are highly expressed in multiple types of tumors. This study aimed to synthesize, preclinically evaluate, and clinically validate a novel dual-targeted PET imaging probe ⁶⁸Ga-pentixafor-c(RGDfK) for its potential in imaging tumors.

The effects of ⁶⁸Ga-pentixafor-c(RGDfK) on cell viability, targeting specificity, and affinity were assessed in the U87MG cells. Micro-PET/CT imaging and biodistribution studies were conducted in U87MG tumor-bearing BALB/c nude mice to evaluate the probe's in vivo pharmacokinetics. A prospective analysis was conducted on patients who underwent both ⁶⁸Ga-pentixafor-c(RGDfK) PET/CT and ¹⁸F-FDG PET/CT. The results obtained from the two imaging modalities were compared.

In vitro, ⁶⁸Ga-pentixafor-c(RGDfK) showed higher uptake activity, targeting specificity, and affinity in U87MG cells than ⁶⁸Ga-pentixafor. In vivo, tumor uptake was higher than in normal tissues (P < 0.05), with renal excretion and low hepatobiliary excretion. Clinical results indicated that ⁶⁸Ga-pentixafor-c(RGDfK) PET/CT had higher sensitivity, specificity, and accuracy in diagnosing primary and metastatic lesions compared to ¹⁸F-FDG PET/CT (93.1% vs. 74.7%, 79.2% vs. 62.5%, 90.1% vs. 72.1%, and 93.2% vs. 74.5%, 84.7% vs. 78%, 89.7% vs. 75.9%). The tumor-to-background ratio (TBR) at 120 min delayed scanning was significantly higher than at 60 min (P < 0.05).

⁶⁸Ga-pentixafor-c(RGDfK) PET/CT demonstrated good safety and clinical feasibility in diagnosing tumors, particularly in differentiating benign and malignant lesions when ¹⁸F-FDG PET/CT results are uncertain.