Abstract
1482
Objectives: We are developing tumor pretargeting using MORF oligomers. We have now applied this technology to the pretargeting of prostate xenografts in mice because of the need for improved prostate cancer detection and because imaging of prostate tumors is particularly challenging. Methods: The B72.3 anti-TAG-72 antibody was conjugated with our standard 18 mer MORF while the complementary cMORF was radiolabeled with Tc99m. The specific binding of the B72.3 antibody to CWR22 prostate tumor fragments was first confirmed by placing the In111 labeled antibody in competition with increasing concentrations of the native antibody. The antibody biodistribution when administered IV at 30 ug was then determined at 3 days in nude mice bearing CWR22 tumors. Thereafter, tumored mice received IV the unlabeled MORF-B72.3 at the same 30 ug dosage and, 3 days later, received IV the Tc99m-cMORF at a dosage selected from earlier experience in the pretargeting of LS174T tumor bearing mice. At 3 h post radioactivity administration, the animals were sacrificed for biodistribution. As controls, an identical group of tumored mice received the radiolabeled cMORF but not the antibody. To obtain both SPECT (HiSPECT, Bioscan) and planar images, one animal received a higher radioactivity dosage. Results: The B72.3 antibody bound specifically to the CWR22 tumor to confirm the presence of TAG-72 expression. The pharmacokinetics of the antibody provided a tumor accumulation of 4.28 %ID/g at 3 days. The tumor accumulation at 3 h of Tc99m-cMORF in the study animals averaged 1.81 %ID/g compared to only 0.12 %ID/g in the control animals, confirming that the MORF-B72.3 in tumor was accessible to the radiolabeled cMORF. Both the SPECT and planar images showed activity only in tumor and kidneys apart from bladder. The tumor/normal tissue ratios obtained by pretargeting at 3 h were comparable or superior in most tissues to those obtained at 3 d in the In111 labeled antibody study. Conclusions: Prostate cancer xenograft in mice was imaged successfully by MORF pretargeting.
- Society of Nuclear Medicine, Inc.