Alteration of the Pharmacokinetics of Small Proteins by Iodination

Pharmacokinetics and Organ Distribution of Cationized Colchicine-Specific IgG and Fab Fragments in Rat

“…A similar perturbation in the pharmacokinetics of epidermal growth factor, with a molecular weight of about 6 kDa, was attributed to molecular change in the protein configuration after radioiodination. 23 These findings had important implications for our study for at least two reasons: first, the molecular weight of Fab, about 50 kDa, is within the range of iodination side effects described by Bauer,22 whereas IgG molecules are far above the side effects range, and, second, cationization could also have an influence on protein stability following radioiodination. For these reasons, cationized and native antibodies iodinated by the Iodogen method were measured in rat plasma by both TCA precipitation and immunoprecipitation in a satellite group of rats.…”

“…A similar percentage of 98% of free iodine in the urinary excretion of cationized albumin has been reported by Bergmann et al 24 However, although thyroid has a high affinity for free 125 I, we did not observe significant differences in iodine uptake by the thyroid for cIgG or cFab compared with nIgG and nFab. These data confirm the previous observation of Bauer 22 that high molecular weight radioiodinated proteins, such as IgG, are more stable than smaller proteins, such as Fab fragments. In addition, we also found that cationized IgG and Fab are more sensitive to deiodination than native antibodies, especially during the distribution phase.…”

“…These drawbacks have been documented by Bauer et al 22 who compared the pharmacokinetics of recombinant proteins with molecular weights ranging from 23 kDa to 80 kDa, which were either radiolabeled by iodine 125 I or quantified by specific immunoassay. This study revealed that the pharmacokinetics of proteins below about 60 kDa were different when assayed by radioactivity or immunoassay, but those proteins with a molecular weight of at least 80 kDa showed only minimal differences.…”

Perturbation of Epidermal Growth Factor Clearance after Radioiodination and Its Implications

“…Examples of in vivo deiodination have been illustrated for some exogenous peptides and proteins. 41,42 The difference in disposition between radioiodinated and unlabeled materials is particularly outstanding and unique with epidermal growth factors, although a few similar but smaller inconsistencies have been seen with human growth hormone, 43 transforming growth factor 1, 44 insulin, 45 tissue plasminogen activator, 46 bactericidal/permeability increasing protein, 51 (Also see refs 51 and 52.) and tumor necrosis factor.…”

La cationisation, un procédé de vectorisation des anticorps dans le système nerveux central

“…Or, la modification chimique d'une protéine peut entraîner une altération de son comportement ciné tique. Un catabolisme accru des protéines peut être observé après leur radiomarquage à l'iode [64,65]. La formation de produits du métabolisme peut altérer la mesure des concentrations de la protéine dans le sang ou les extraits tissulaires, et conduire à une estimation erro née de ses paramètres cinétiques et de sa capture dans les tissus.…”