Physiological biodistribution of 68Ga-Pentixafor: PET/CT evaluation and implications for CXCR4 imaging.
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PURPOSE: 68Ga-Pentixafor PET/CT is a novel imaging modality targeting the C-X-C chemokine receptor type 4 (CXCR4), which plays a crucial role in immune regulation, stem cell homing, and tumor progression. While its clinical use is expanding, comprehensive characterization of its physiological biodistribution remains limited. METHODS: This study retrospectively included 73 individuals who underwent 68Ga-Pentixafor PET/CT, comprising patients with various benign and malignant conditions, as well as healthy volunteers. Time-activity curves (TACs) were generated in two volunteers with dynamic and static imaging at multiple timepoints. Semi-quantitative uptake metrics (SUVmax and SUVmean) were measured across normal organs and tissues. Age- and sex-related uptake patterns were analyzed in the cohort. Moreover, a subgroup of 12 participants underwent dual-timepoint imaging at 30 and 60 min post-injection of 68Ga-Pentixafor was analyzed. RESULTS: 68Ga-Pentixafor demonstrated primarily urinary clearance with intense radiotracer accumulation in the kidneys and bladder, and displayed obvious physiological uptake in the nasopharynx, palatine tonsils, thymus, spleen, adrenal glands, and pediatric bone. Males showed higher muscle SUVmax than females (P = 0.036), while females displayed higher thymus SUVmax and SUVmean than males (both P < 0.001). Pediatric subjects exhibited higher radiotracer uptake in the nasopharynx, thymus and bone than adults (P < 0.05), whereas adults demonstrated higher radioactivity uptake in the thyroid, stomach, prostate, testes, and muscle than children (P < 0.05). Moreover, significantly lower radiotracer uptake was observed at 60 min compared to 30 min post-injection in the nasopharynx, parotid glands, lungs, blood pool, spleen, pancreas, kidneys, bone, and muscle (P < 0.05). This suggested that imaging at 60 min provided superior target-to-background contrast compared to 30 min. CONCLUSIONS: 68Ga-Pentixafor exhibited significant physiological uptake in nasopharynx, palatine tonsils, thymus, spleen, adrenal glands, pediatric bone, kidneys, and bladder. Semi-quantitative uptake values varied with sex, age and imaging time. These findings provided essential guidance for interpreting CXCR4-targeted PET/CT imaging.