Immuno-PET of undifferentiated thyroid carcinoma with radioiodine-labelled antibody cMAb U36: application to antibody tumour uptake studies.
OBJECTIVE
We tested the suitability of the chimeric monoclonal anti-human CD44 splice version 6 antibody (cMAb U36) for targeting and visualising human anaplastic thyroid carcinoma with PET. We also performed experiments aimed at elucidating the relation between tumour interstitial fluid pressure (TIFP) and the tumour uptake of antibodies.


METHODS
The affinity and specificity of the cMAb U36 for KAT-4 cells were evaluated in vitro, as was the Na+/I- symporter (NIS) expression. Biodistribution studies were performed on KAT-4 carcinoma-bearing mice injected with 124I-cMAb U36 or free iodine. Biodistribution studies were also performed in animals treated with the specific TGF-beta1 and -beta3 inhibitor Fc:TbetaRII, which lowers TIFP. Treated and non-treated animals were scanned by microPET.


RESULTS
Cultured human undifferentiated/anaplastic thyroid carcinoma KAT-4 cells expressed low levels of NIS and uptake of free iodine was insignificant. The cMAb U36 expressed an affinity (KD) of 11+/-2 nM. Tumour radioactivity uptake reached maximum values 48 h after injection of 124I-cMAb U36 (approximately 22%IA/g). KAT-4 carcinomas were readily identified in all 124I-immuno-PET images. Radioactivity tumour uptake in Fc:TbetaRII-treated animals was significantly lower at 24 and 48 h after injection, and five times higher thyroid uptake was also noted.


CONCLUSIONS
We successfully used 124I-cMAb U36 to visualise CD44v6-expressing human anaplastic thyroid carcinoma. Given the lack of NIS expression in KAT-4, tumour visualisation is not due to free iodine uptake. Lowering the TIFP in KAT-4 carcinomas did not increase the uptake of mAbs into tumour tissue.
Fortin
Marc-André
MA
Laboratory for Biomaterials and Bioengineering, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, G1K 7P4, Canada. fortin@ifm.liu.se
Salnikov
Alexei V
AV
Nestor
Marika
M
Heldin
Nils-Erik
NE
Rubin
Kristofer
K
Lundqvist
Hans
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D011863:Radioimmunoassay / Q000379:methods; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000473:pathology
C525984:(124)I-cMAb U36; D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors; D007457:Iodine Radioisotopes