68Ga labeled integrin a2b1 tracer for potential phenotyping imaging of metastatic prostate cancer

Objectives The ability to early detect and assess the treatment respond of recurrent and/or disseminated metastatic prostate cancer is critical for the effective management of this group of patients. Accumulating experimental evidence indicates that integrin α2β1 might be a prognostic biomarker for advanced phenotype of prostate cancer. In this study, a novel 68Ga-labeled integrin α2β1-targeted PET tracers (68GaA2B1) were designed and evaluated for the imaging of prostate cancer.

Methods To prospectively verify the prognostic value of 68GaA2B1, the comparisons of 68GaA2B1, 11C-acetate and FDA approval 11C-choline positron emission tomography (PET) were performed in subcutaneous PC-3 (integrin positive; bone metastatic) and CWR22rv (integrin negative) at 15min post-injection after injection of 7-8MBq tracers. The biodistribution of tracers was also determined at 30 min post-injection in tumor-bearing athymic mice. The average radioactivity accumulation within a tumor or an organ was quantified from the multiple region of interest volumes using the %ID/g value and were analyzed in accordance with the pathologic data.

Results The 68GaA2B1 uptake in malignancies (PC-3) was 1.68%ID/g (n=4), which was significantly higher than that in relatively benign prostate tumor lesions CWR22rv (0.57%ID/g; n=4); the accumulation of 11C-acetate and 11C-choline in PC-3 was 2.64 %ID/g ( n=4) and 1.65 %ID/g (n=4); however, the ratios of tumor/muscle (T/M) in PC-3 tumor model were 3.18 (68GaA2B1), 1.5 (11C-acetate) and 1.62 (11C-choline), respectively. These results suggest that there are significant differences in 68GaA2B1 accumulation when comparing with two clinical usage11C labeled PET tracers, and these differences might offer a critical diagnostic imaging criterion in the identification of aggress phenotype of prostate cancer.

Conclusions 68Ga labeled 68GaA2B1allows noninvasive imaging of tumor-associated α2β1 expression, which may represent a useful and easy access PET tracer for evaluation of disease course and therapeutic efficacy at the earliest stages of treatment.