Concurrent radiotherapy and tumor targeting with 111In-HMFG1-F(ab')2 in patients with MUC1-positive non-small cell lung cancer

Anticancer Res. 2005 Nov-Dec;25(6C):4663-71.

Abstract

Background: Combining external radiotherapy (XRT) and radioimmunotargeting might enhance tumor radiation without affecting morbidity, due to different toxicity profiles.

Aim: To assess 111In-F(ab')2-HMFG1 biodistribution, the influence of "low-dose" lysine on F(ab')2 renal uptake and provide data forfurther concurrent XRT and RIT.

Patients and methods: Twenty-three patients received injections of 111n-HMFG1-F(ab')2, with or without lysine co-infusion, 7 and 21 days after the initiation of XRT. Whole-body images, blood and urine activity were monitored.

Results: Despite clear visualization of 111In-F(ab')2-HMFG1, the residence time and absorbed dose in tumors were low. The co-infusion of "low-dose" lysine did not reduce renal uptake, thus contradicting previously published results. The biodistribution differences after the first and the second injection might be attributed to human anti-mouse antibody (HAMA) response or Ag-complexation.

Conclusion: Low-dose lysine is not feasible. Larger amounts of lysine during extended infusion time are therefore advocated. It is proposed that repeated MAb injection be given during the first fractions of XRT.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Amino Acids / therapeutic use
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Humans
  • Immunoglobulin Fragments / metabolism
  • Immunoglobulin Fragments / therapeutic use
  • Indium Radioisotopes / pharmacokinetics
  • Indium Radioisotopes / therapeutic use*
  • Isothiocyanates / pharmacokinetics
  • Isothiocyanates / therapeutic use
  • Kidney / metabolism
  • Liver / metabolism
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Lysine / analogs & derivatives
  • Lysine / therapeutic use
  • Middle Aged
  • Molecular Sequence Data
  • Mucin-1 / biosynthesis
  • Mucin-1 / metabolism*
  • Neoplasm Staging
  • Pentetic Acid / analogs & derivatives
  • Pentetic Acid / pharmacokinetics
  • Pentetic Acid / therapeutic use
  • Radioimmunotherapy / methods
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use*
  • Tissue Distribution

Substances

  • 6-(4-isothiocyanatobenzyl)-diethylenetriamine pentaacetic acid
  • Amino Acids
  • Antibodies, Monoclonal
  • Immunoglobulin Fragments
  • Indium Radioisotopes
  • Isothiocyanates
  • Mucin-1
  • Radiopharmaceuticals
  • pemtumomab
  • Pentetic Acid
  • Lysine