Advantage of a residualizing iodine radiolabel for radioimmunotherapy of xenografts of human non-small-cell carcinoma of the lung.

Abstract

UNLABELLED:

Attachment of 131I to MAbs through adducts such as dilactitol-tyramine (DLT), which remain lysosomally trapped after catabolism of the labeled MAb, can greatly increase the residence time of the radiolabel at the tumor site. Our previous studies demonstrated a marked increase in accretion of 131I in a human lung-cancer xenograft model, using 131I-DLT in comparison to 131I linked to MAb by the conventional chloramine-T methodology.

METHODS:

In this study, biodistribution experiments were performed to evaluate the effect of protein dose on the accretion of 131I-DLT-labeled MAb RS11 in tumor and nontumor tissues, and in vivo radioimmunotherapy experiments compared the effect of single injections of 131I-DLT-labeled MAb RS11 to conventional 131I-labeled RS11 and an untreated control group.

RESULTS:

Dosimetry calculations based on the biodistribution data indicate only small changes in absorbed dose-to-tumor and nontumor tissues with increasing protein dose up to 100 micrograms, with a predicted absorbed dose to tumor of from 21,000 to 25,000 cGy/mCi. A single dose of 100 microCi of 131I-DLT-RS11 was found to cause tumor regression. At 7 wk postinjection of the radiolabeled MAbs, tumor volume in 73% of the animals administered 131I-DLT-labeled RS11 remained smaller than at the time of MAb injection. This is compared to 14% of the tumors in the conventionally labeled 131I-RS11 group and none in the untreated group.

CONCLUSION:

The use of the residualizing radiolabel DLT provides a therapeutic advantage in comparison to conventional 131I-labeled RS11.

• Authors: R Stein, D M Goldenberg, S R Thorpe, M J Mattes
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 38 Issue 3 Pg. 391-5 (Mar 1997) ISSN: 0161-5505 [Print] United States
• PMID: 9074526 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Biomarkers, Tumor
• Iodine Radioisotopes
• dilactitol tyramine
• Tyramine

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, pharmacokinetics)
• Biomarkers, Tumor (pharmacokinetics)
• Carcinoma, Non-Small-Cell Lung (diagnostic imaging, metabolism, radiotherapy)
• Female
• Humans
• Iodine Radioisotopes (pharmacokinetics, therapeutic use)
• Lung Neoplasms (diagnostic imaging, metabolism, radiotherapy)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Radioimmunotherapy
• Radionuclide Imaging
• Radiotherapy Dosage
• Remission Induction
• Tissue Distribution
• Transplantation, Heterologous
• Tyramine (administration & dosage, analogs & derivatives, pharmacokinetics)