99MTC Alpha-Fetoprotein: A Novel, Specific Agent for the Detection of Human Breast Cancer

摘要

Because adenocarcinoma of the breast expresses receptors for alpha- fetoprotein (AFP), we studied Tc-99m radiolabeled AFP and its sub domains as agents to detect breast cancer. The biodistribution of Tc-99m radiolabeled natural (full length) and recombinant domain III (DIII) of human AFP was compared to the clinical agents Tc-99m sestamibi and Tl-20l in a murine model of human breast cancer. Estrogen receptor positive (MCF-T, T47, MTW9A) and estrogen receptor negative (MDA MB-23l, BT2O) human breast cancer xenografts were grown subcutaneously in the lateral thorax region of immunosuppressed mice (CB-17 SCID) Quantitative comparisons of percent-injected dose per gram of tissue (%ID/ gram) and tumor to thigh ratio (T/Th) were performed at 0-60 minutes and at 24 hours following injection. For most tumors, T/Th for AFP and DIII was significantly greater than T/Th for Tc-99m sestamibi and Tl-201. DIII and AFP had significantly higher ID/gram than either Tl-20l or Tc-99m sestamibi when considered across all tumor types (BT2O, MCF7, MDA, MTW9A, T4T) at both 60 minutes and 24 hours. In the final year of the work we showed similar properties for a 12 amino acid peptide derived from AFP. The data suggests that localization of Tc-99m AFP in human breast cancer xenografts is initially rapid, increases with time, and is superior to Tc-99m sestamibi and Tl-201. Given its high uptake by breast cancer cells, its low non-tumor localization and its rapid renal excretion, these Tc-99m AFP preparations should be useful agents to detect human breast carcinoma.