Rapid imaging of human melanoma xenografts using an scFv fragment of the human monoclonal antibody H11 labelled with 111In.
H11 is a human IgM monoclonal antibody which recognizes a novel tumour-associated antigen expressed on melanoma, glioma, breast cancer, colon cancer, prostate cancer, lung cancer and B-cell lymphoma. In this study, a recombinant single-chain Fv (scFv) fragment of H11 labelled with 111In was investigated for tumour imaging in athymic mice implanted subcutaneously with A-375 human melanoma xenografts. H11 scFv was derivatized with diethylenetriaminepentaacetic acid (DTPA) for labelling with 111In. The immunoreactivity of DTPA-H11 scFv against A-375 cells in vitro ranged from 23% to 36%. 111In-DTPA-H11 scFv was rapidly eliminated from the blood and most normal tissues (except the kidneys) reaching maximum tumour/blood ratios of 12:1 at 48 h post-injection. Tumours were imaged as early as 40 min after injection. The kidneys accumulated the highest concentration of radioactivity (up to 185% injected dose/g). Tumour uptake was 1-3% injected dose/g. The whole-body radiation absorbed dose predicted for administration of 185 MBq of 111In-DTPA-H11 scFv to humans was 37 mSv. The radiation absorbed dose estimates for the kidneys, spleen and intestines were 405 mSv, 698 mSv and 412 mSv, respectively. The results of this preclinical study and a concurrent phase I trial suggest a promising role for H11 scFv for tumour imaging.
Reilly
R M
RM
Division of Nuclear Medicine, Toronto General Hospital, University Health Network, ON, Canada. raymond.reilly@utoronto.ca
Maiti
P K
PK
Kiarash
R
R
Prashar
A K
AK
Fast
D G
DG
Entwistle
J
J
Dan
Narang
S A
SA
Foote
S
S
Kaplan
H A
HA
D000818:Animals; D000911:Antibodies, Monoclonal; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007700:Kinetics; D008545:Melanoma / Q000000981:diagnostic imaging*; D051379:Mice; D008819:Mice, Nude; D004369:Pentetic Acid; D016719:Radioimmunodetection / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D004369:Pentetic Acid