Pretargeted radioimmunotherapy (RIT) with a novel anti-TAG-72 fusion protein

Cancer Biother Radiopharm. 2005 Aug;20(4):379-90. doi: 10.1089/cbr.2005.20.379.


Pretargeted radioimmunotherapy (RIT) increases the dose of radionuclide delivered to tumor sites while limiting radiation to normal tissues. The three components in Pretarget include a streptavidin-containing targeting molecule, a synthetic clearing agent (sCA), and (90)Y and/or (111)In-DOTA-biotin. This trial determined the feasibility and safety of using a genetically engineered fusion protein directed to TAG-72 as the targeting agent. Nine (9) patients with metastatic colorectal cancer (TAG-72+) received 160 mg/m(2) of CC49Fusion protein intravenously (i.v.), followed by the sCA, 45 mg/m(2) i.v. Twenty-four (24) hours later, patients received radiolabeled DOTA-biotin (either 0.65 or 1.3 mg/m(2)). All patients received 5 mCi of (111)In-DOTA-biotin for imaging and dosimetry purposes and patients 4-9 received 10 mCi/m2 of (90)Y-DOTA-biotin as well. The mean plasma T1/2 of CC49Fusion protein was 23 +/- 6 hours. Greater than 95% of the circulating CC49Fusion protein was eliminated from the circulation within 6 hours of sCA administration. The radiolabeled DOTA-biotin rapidly localized to tumor sites while the unbound fraction was rapidly excreted. The mean tumor-to-marrow radiation dose ratio was 139:1 and mean tumor: whole body was 56:1. No infusion-related, renal, hepatic, or hematologic toxicities were noted. CC49Fusion protein performs well in a pretargeted RIT schema, and further study with escalating doses of (90)Y should be pursued. This strategy has the potential to deliver effective radiation tumor doses to TAG- 72+ tumors.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / therapy
  • Aged
  • Antigens, Neoplasm / therapeutic use*
  • Biotin / analogs & derivatives
  • Biotin / chemistry
  • Biotin / pharmacology
  • Clinical Trials as Topic
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gamma Cameras
  • Gastrointestinal Neoplasms / therapy
  • Glycoproteins / therapeutic use*
  • Humans
  • Indium Radioisotopes
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Organometallic Compounds / pharmacology
  • Radioimmunotherapy / methods*
  • Radioisotopes
  • Radiometry
  • Radiopharmaceuticals / therapeutic use
  • Recombinant Fusion Proteins / chemistry*
  • Rhenium
  • Streptavidin / pharmacology
  • Time Factors
  • Treatment Outcome
  • Yttrium Radioisotopes / therapeutic use


  • Antigens, Neoplasm
  • DOTA-biotin
  • Glycoproteins
  • Indium Radioisotopes
  • Organometallic Compounds
  • Radioisotopes
  • Radiopharmaceuticals
  • Recombinant Fusion Proteins
  • Yttrium Radioisotopes
  • tumor-associated antigen 72
  • Biotin
  • Rhenium
  • Streptavidin