Targeting Human Prostate Cancer PC3 with Bombesin-Anti-DTPA Fab Bispecific Complexes and DTPA-polymer-drug conjugates for Molecular Imaging and Therapy

Vishwesh Patil1, Keyur Gada1, Rajiv Panwar1, Alexandra Varvarigou2, Stan Majewski3, Yared Tekabe4, Ban-An Khaw1.

1Northeastern University, Boston, MA, 2Demokritos Institute of Radioisotopes, Athens, Greece, 3University of West Virginia, Morgantown, WV, 4Columbia University Medical center, New York, NY. b.khaw@neu.edu

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Summary
Pretargeting human prostate cancer PC3 xenografts with Bispecific Bombesin anti-diethylene triamine penta acetic acid (DTPA) Fab Complexes (BBAFCx) and targeted with Tc-99m labeled DTPA-succinylated polylysine (DSPL) enabled molecular imaging of small prostate cancer lesions (1.5x1 mm lesions, 6.54±1.58 %ID/g). Pretargeting with Bombesin alone showed no uptake of the radiolabeled polymers in tumors (0.44±0.17). When radiolabeled polymers were replaced with DTPA-Doxorubicin-poly-l-glutamic acid (D-Dox-PGA) and PC3 cells pretargeted with Bispecific Bombesin-Anti-DTPA antibody Complex (BBACx), in vitro tumor toxicity was greater than free Dox toxicity by 2 fold. Pretargeting approach using polymer-drug-conjugates enhances molecular imaging and targeted cancer therapy.

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