Imaging prostate cancer PC-3 xenografts with In-111-polymer-drug conjugates after pretargeting with Bombesin-bispecific antibody complexes

Objectives Human prostate cancer PC-3 are pretargeted with Bom-bispecific antibody complex (BBAC) and targeted with high specific activity In-111-labeled polymers (In-111-DSPL) to visualize very small lesions.

Methods PC-3 human prostate cancer xenografted mice with small lesions were injected i.v. with 10 μg of BBAC (n=4) or Bombesin (Bom) (n=5); 24 hours later, mice were injected with 7.03+1.74 and 6.88+1.89 MBq In-111-DSPL respectively. Planar or SPECT/CT gamma images were obtained for up to 3 hours and only planar images at 24 hours. The animals were killed and biodistribution of the radiotracer determined by gamma scintillation counting.

Results SPECT/CT imaging allowed detection of PC-3 prostate cancer lesions less than 1 mm in diameter in 1-3 hours post In-111-DSPL injection. Planar gamma imaging with a 3mm pin-hole collimator, lesions were visualized by 3 hours. No lesions were visualized in Bom controls. Tumor activity of 1.21+0.36 %ID/g in pretargeted tumors was 5.4 times that of In-111-DSPL activity in control tumors (0.22+0.08, p =0.001). Other organ activities are significantly less than tumor activity of mice pretargeted In-111 DSPL injected mice (p = 0.0016-0.026).

Conclusions Pretargeting prostate cancer PC-3 with BBAC allowed fast delivery of high specific radioactivity In-111-polymer drug conjugates allowing visualization of lesions smaller than 1 mm in diameter within 3 hours.

Research Support Discretionary funds of the lab