Unknown

Dataset Information

0

Monodispersed DOTA-PEG-conjugated anti-TAG-72 diabody has low kidney uptake and high tumor-to-blood ratios resulting in improved 64Cu PET.


ABSTRACT: Diabodies are noncovalent dimers of single-chain antibody fragments that retain the avidity of intact IgG but have more favorable blood clearance than intact IgG. Radiometals offer a wide range of half-lives and emissions for matching imaging and therapy requirements and provide facile labeling of chelate-antibody conjugates. However, because of their high retention and metabolism in the kidney, the use of radiometal-labeled diabodies can be problematic for both imaging and therapy.Having previously shown that (111)In-DOTA-polyethylene glycol (PEG)3400-anti-carcinoembryonic antigen diabody has less than half the kidney uptake and retention of non-PEGylated diabody and that the two have similarly high tumor uptake and retention, we synthesized a similar derivative for an anti-tumor-associated glycoprotein 72 diabody. We also reduced the molecular size of the polydispersed PEG3400 to monodispersed PEG27 and PEG12 (nominal masses of 1,321 and 617, respectively). We performed biodistributions of their DOTA conjugates radiolabeled with (125)I, (111)In, or (64)Cu in tumor-bearing athymic mice.The addition of PEG3400 to the diabody reduced kidney uptake to a level (approximately 10 percentage injected dose/g) comparable to that obtained with radiometal-labeled intact IgG. The PEG27 and PEG12 diabody conjugates also demonstrated low kidney uptake without reduction of tumor uptake or tumor-to-blood ratios. When radiolabeled with (64)Cu, the DOTA-PEG12 and -PEG27 diabody conjugates gave high-contrast PET images of colon cancer xenografts in athymic mice.PEGylated diabodies may be a valuable platform for delivery of radionuclides and other agents to tumors.

SUBMITTER: Li L 

PROVIDER: S-EPMC3247072 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Monodispersed DOTA-PEG-conjugated anti-TAG-72 diabody has low kidney uptake and high tumor-to-blood ratios resulting in improved 64Cu PET.

Li Lin L   Turatti Fabio F   Crow Desiree D   Bading James R JR   Anderson Anne-Line AL   Poku Erasmus E   Yazaki Paul J PJ   Williams Lawrence E LE   Tamvakis Debra D   Sanders Paul P   Leong David D   Raubitschek Andrew A   Hudson Peter J PJ   Colcher David D   Shively John E JE  

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20100616 7


<h4>Unlabelled</h4>Diabodies are noncovalent dimers of single-chain antibody fragments that retain the avidity of intact IgG but have more favorable blood clearance than intact IgG. Radiometals offer a wide range of half-lives and emissions for matching imaging and therapy requirements and provide facile labeling of chelate-antibody conjugates. However, because of their high retention and metabolism in the kidney, the use of radiometal-labeled diabodies can be problematic for both imaging and th  ...[more]

Similar Datasets

| S-EPMC6215696 | biostudies-literature
| S-EPMC5906006 | biostudies-literature
| S-EPMC6911626 | biostudies-literature
| S-EPMC3057960 | biostudies-literature
| S-EPMC7868933 | biostudies-literature
| S-EPMC3614955 | biostudies-literature
| S-EPMC4217715 | biostudies-literature
| S-EPMC3955276 | biostudies-literature
| S-EPMC5885140 | biostudies-literature
| S-EPMC5499097 | biostudies-literature