title: Scintigraphic detection of breast cancer xenografts with Tc-99m natural and recombinant human alpha-fetoprotein.
abstract: Because adenocarcinoma of the breast expresses receptors for alpha-fetoprotein (AFP), we studied Tc-99m AFP as a radiopharmaceutical to detect breast cancer. The biodistribution of Tc-99m radiolabeled natural human AFP (full length) and recombinant domain III (DIII) of human AFP was compared to Tc-99m sestamibi and Tl-201 in a murine model of human breast cancer. Estrogen receptor positive (MCF7, T-47D) and estrogen receptor negative (MDA-MB-231, BT-20) human breast cancer xenografts were grown subcutaneously in the lateral thorax region of immunosuppressed mice (ICR 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. In all breast cancers (BT-20, MCF7, MDA-MB-231, T-47D), Tc-99m AFP T/Th increased from 60 minutes to 24 hours, suggesting good tumor retention of this radiopharmaceutical. DIII and AFP had significantly higher %ID/gram than either Tl-201 or Tc-99m sestamibi when considered across all tumor types at both 60 minutes and 24 hours. 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 may be useful agents to detect human breast carcinoma.
authors.affiliation: Department of Radiology, Albany Medical Center, NY 12208, USA. bline@ccgateway.amc.edu
authors.forename: B R
authors.initials: BR
authors.lastname: Line
authors.forename: P J
authors.initials: PJ
authors.lastname: Feustel
authors.forename: S M
authors.initials: SM
authors.lastname: Festin
authors.forename: T T
authors.initials: TT
authors.lastname: Andersen
authors.forename: R N
authors.initials: RN
authors.lastname: Dansereau
authors.forename: R L
authors.initials: RL
authors.lastname: Lukasiewicz
authors.forename: S
authors.initials: S
authors.lastname: Zhu
authors.forename: J A
authors.initials: JA
authors.lastname: Bennett
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D006528:Carcinoma, Hepatocellular; D005260:Female; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011960:Receptors, Estrogen / Q000032:analysis; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013667:Technetium / Q000493:pharmacokinetics; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics; D013794:Thallium Radioisotopes; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000493:pharmacokinetics
chemical_list: D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D013794:Thallium Radioisotopes; D000509:alpha-Fetoproteins; D013667:Technetium; D017256:Technetium Tc 99m Sestamibi