IMMUNOSCINTIGRAPHY OF HUMAN COLON-CANCER XENOGRAFTS IN NUDE-MICE USING A 2ND-GENERATION TAG-72 MONOCLONAL-ANTIBODY LABELED WITH (99)TC(M)

Monoclonal antibody CC83 is a second-generation high-affinity antibody directed against the TAG-72 antigen in colorectal cancer. Our objecti ves were to evaluate the biodistribution, pharmacokinetics and imaging properties of CC83 labelled with Tc-99m via a modified Schwartz techn ique. The immunological integrity of Tc-99m-CC83 was evaluated by size -exclusion FPLC and by determining the immunoreactive fraction in vitr o against bovine submaxillary mucin. The biodistribution of Tc-99m-CC8 3 up to 24 h postinjection was evaluated in nude mice bearing subcutan eous LS174T human colon cancer xenografts. Blood radioactivity data wa s fitted to a one-compartment pharmacokinetic model. Images of tumour- bearing mice were obtained at 17-24 h postinjection with Tc-99m-CC83. Tc-99m-CC83 was eluted as intact immunoglobulin by FPLC analysis and t he mean immunoreactive fraction was 0.49 +/- 0.15. Tumour uptake at 24 h postinjection was 11.2 +/- 4.1 % i. d. g-1. Radioactivity in the bl ood was eliminated rapidly with a half-life of 8 h and tumour:blood ra tios were >2:1 at 24 h postinjection. LS174T tumours were successfully imaged in 3/3 mice, In vitro studies showed instability of Tc-99m-CC8 3 when challenged with cysteine and glutathione but not metallothionei n, suggesting a metabolic route for the Tc-99m antibody in vivo. We co nclude that CC83 labelled directly with Tc-99m retains its immunologic al integrity and capability specifically to target subcutaneous LS174T human colon cancer tumours hosted in nude mice. These results further suggest that Tc-99m-CC83 may have potential for imaging colorectal ca ncer in humans.