Two-step radio-immunotargeting of renal-cell carcinoma xenografts in nude mice with anti-renal-cell-carcinoma X anti-DTPA bispecific monoclonal antibodies

Int J Cancer. 1998 Jan 5;75(1):74-80. doi: 10.1002/(sici)1097-0215(19980105)75:1<74::aid-ijc12>3.0.co;2-d.

Abstract

The specificity of antibodies offers unique opportunities to target tumors with radionuclides. However, due to the slow clearance of radiolabeled antibody, relatively high back-ground is observed in non-target organs. Pre-targeting protocols using bispecific monoclonal antibodies (bsMAbs) and radiolabeled chelates may overcome this problem. We have evaluated the anti-renal-cell-carcinoma (RCC) X anti-DTPA bsMAb G250 x DTIn1 for 2-step targeting of RCC tumors in nude mice. Tumor uptake of 111In-DTPA was similar up to a 3-day interval between bsMAb and 111In-DTPA injections and decreased thereafter. The effect of G250 x DTIn1 protein dose was studied. High tumor uptake was seen at 1 to 4 micrograms, whereas at higher doses uptake decreased. Tumor was saturated with 15 micrograms bsMAb. At the saturating bsMAb dose the 111In-DTPA amount was varied. High tumor uptake was observed at a 10-fold molar excess 111In-DTPA, whereas at higher excess uptake decreased. After priming with 15 micrograms bsMAb and targeting with a 10-fold molar excess 111In-DTPA, the biodistribution of 111In-DTPA was studied for 1 to 48 hr after injection. Good tumor retention of 111In-DTPA was observed, while the radiolabel cleared rapidly from the blood. Consequently, tumor-to-blood ratios increased with time to 500 at 24 hr after injection. In conclusion, RCC xenografts can be targeted efficiently using G250 x DTIn1 and 111In-DTPA. However, this requires careful tuning of bsMAb protein dose and 111In-DTPA dose. Using the optimal protein dose and 111In-DTPA dose, high 111In-DTPA tumor uptake and tumor-to-blood ratios can be obtained, thus providing good perspectives for diagnostic and therapeutic use in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / pharmacokinetics
  • Antibodies, Bispecific / therapeutic use*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / radiotherapy*
  • Humans
  • Indium Radioisotopes / pharmacokinetics
  • Indium Radioisotopes / therapeutic use*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / radiotherapy*
  • Mice
  • Pentetic Acid*
  • Radioimmunotherapy / methods*
  • Tissue Distribution
  • Transplantation, Heterologous

Substances

  • Antibodies, Bispecific
  • Indium Radioisotopes
  • Pentetic Acid