Optimizing lutetium 177-anti-carbonic anhydrase IX radioimmunotherapy in an intraperitoneal clear cell renal cell carcinoma xenograft model

Mol Imaging. 2014;13:1-7.

Abstract

A new approach in the treatment of clear cell renal carcinoma (ccRCC) is radioimmunotherapy (RIT) using anti-carbonic anhydrase IX (CAIX) antibody G250. To investigate the potential of RIT with lutetium 177 (177Lu)-labeled G250, we conducted a protein dose escalation study and subsequently an RIT study in mice with intraperitoneally growing ccRCC lesions. Mice with intraperitoneal xenografts were injected with 1, 3, 10, 30, or 100 μg of G250 labeled with 10 MBq indium 111 (111In) to determine the optimal protein dose. The optimal protein dose determined with imaging and biodistribution studies was used in a subsequent RIT experiment in three groups of 10 mice with intraperitoneal SK-RC-52 tumors. One group received 13 MBq 177Lu-DOTA-G250, a control group received 13 MBq nonspecific 177Lu-MOPC21, and the second control group was not treated and received 20 MBq 111In-DOTA-G250. The optimal G250 protein dose to target ccRCC in this model was 10 μg G250. Treatment with 13 MBq 177Lu-DOTA-G250 was well tolerated and resulted in significantly prolonged median survival (139 days) compared to controls (49-53 days, p = .015), indicating that RIT has potential in this metastatic ccRCC model.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / radiotherapy*
  • Cell Line, Tumor
  • Coordination Complexes / therapeutic use
  • Dose-Response Relationship, Radiation
  • Heterocyclic Compounds, 1-Ring / therapeutic use
  • Heterografts
  • Humans
  • Immunoconjugates / administration & dosage*
  • Immunoconjugates / pharmacokinetics
  • Immunoconjugates / therapeutic use
  • Injections, Intraperitoneal
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / radiotherapy*
  • Lutetium / therapeutic use*
  • Maximum Tolerated Dose
  • Mice
  • Neoplasm Transplantation
  • Neoplasms, Experimental
  • Radioimmunotherapy
  • Radioisotopes / therapeutic use*
  • Radiopharmaceuticals / administration & dosage*
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Coordination Complexes
  • G250 monoclonal antibody
  • Heterocyclic Compounds, 1-Ring
  • Immunoconjugates
  • Radioisotopes
  • Radiopharmaceuticals
  • indium-111-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
  • Lutetium