Abstract
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Objectives: A panel of phage antibodies has been generated by selection of phage antibody display libraries against tumor cells in situ on both fresh frozen and paraffin-embedded tissues using laser capture microdissection. In this study, one internalizing single chain antibody (UA20) specific for prostate cancer was labeled with 99mTc and investigated for tumor targeting in human prostate tumor xenograft model.
Methods: UA20 was engineered to contain a hexahistidine tag to accommodate the 99mTc-tricarbonyl labeling (99mTc-UA20). The stability of 99mTc labeling was tested in vitro in mouse serum and phosphate buffer at 37°C for 6 h by both HPLC and TLC. The labeled UA20 and control antibody (N3M2) were administered to athymic mice implanted subcutaneously with the Du-145. Mice were imaged with microSPECT/CT at 1h, 2h and 3h post-injection and sacrificed at 3h to assess biodistribution.
Results: UA20 was labeled in 55-65% yield and remained stable within the incubation time. 99mTc-UA20 was rapidly eliminated from the blood and most normal tissues (except the kidneys) giving tumor/blood and tumor/muscle ratios of 12:1 and 70:1 as early as 3h post-injection. MicroSPECT/CT imaging showed strong tumor and kidney uptake. Tumor was visualizeded as early as 1 h after injection. At 3h post-injection, tumor uptake was only lower than that of kidneys (81%ID/g) at 4.4%ID/g with liver at 2.7%ID/g. The remaining organ/tissue uptakes were lower than 1%ID/g. In contrast, the control antibody only exhibited tumor uptake of 0.26%ID/g similar to muscle and fat and much lower than most other organ/tissues.
Conclusions: UA20 showed strong tumor targeting in the human prostate cancer xenograft model, demonstrating potential use in targeted imaging and therapy against prostate cancer.
- Society of Nuclear Medicine, Inc.