Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET

We recently demonstrated the feasibility of combining enhanced tumor-to-tis sue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was ob tained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the po sitron emitter Ga-68, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesiz ed a BS-MAb from the F(ab')(2) fragments of the anti-MUC1 MAb 12H12 which r eacts with the vast majority of human breast carcinomas, and the F(ab') fra gment of an anti-Ga chelate MAb using a bifunctional chemical linker, The B S-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 10(7) M-1) while the binding capacity of cells was high (8.4 x 10(6) BS-M Abs per cell). Tumor uptake of the Ga-67 labeled chelate in pretargeted ani mals was to 5.8 +/- 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1 h postinjection. This compares with a ratio of 0.65 and 0.85 obtained wi th I-125-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the Ga-68 and Ga-67 labeled chela te was observed. PET imaging of mice, started lh postinjection of the Ga-68 chelate, clearly visualized all tumors, (C) 2001 Elsevier Science Inc. All rights reserved.