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.


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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