Radioiodinated antibody targeting of the HER-2/neu oncoprotein: effects of labeling method on cellular processing and tissue distribution.
Monoclonal antibody (MAb) internalization can have a major effect on tumor retention of radiolabel. Two anti-HER-2/neu MAbs (TA1 and 520C9) were radioiodinated using the iodogen, N-succinimidyl 5-iodo-3-pyridinecarboxylate (SIPC), and tyramine-cellobiose (TCB) methods. Paired-label studies compared internalization and cellular processing of the labeled MAbs by SKOv3 9002-18 ovarian cancer cells in vitro. Intracellular radioiodine activity for 520C9 was up to 2.6 and 3.0 times higher for SIPC and TCB labeling, respectively, compared with iodogen. Likewise, intracellular activity for TA1 was up to 2.3 and 2.9 times higher with the SIPC and TCB methods compared with iodogen labeling. Unfortunately, similar advantages in tumor accumulation were not achieved in athymic mice bearing SKOv3 9008-18 ovarian cancer xenografts.
Zalutsky
M R
MR
Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710, USA. zalut001@mc.duke.edu
Xu
F J
FJ
Yu
Y
Y
Foulon
C F
CF
Zhao
X G
XG
Slade
S K
SK
Affleck
D J
DJ
Bast
R C
RC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics; D002475:Cellobiose / Q000737:chemistry; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009539:Nicotinic Acids / Q000737:chemistry; D010051:Ovarian Neoplasms; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013388:Succinimides / Q000737:chemistry; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D014439:Tyramine / Q000737:chemistry; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry
D000911:Antibodies, Monoclonal; D002475:Cellobiose; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D009539:Nicotinic Acids; D018719:Erb-b2 Receptor Tyrosine Kinases; D013388:Succinimides; D014439:Tyramine; D014508:Urea; C038394:tyramine-cellobiose adduct; C069228:N-succinimidyl-5-iodo-3-pyridinecarboxylic acid; C012385:1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril