Biomedical subjects

Anna Orlova

Publications and source records attributed to Anna Orlova.

22 records · Page 2Linked to original sources

PubMed2002

Comparative biodistribution of the radiohalogenated (Br, I and At) antibody A33. Implications for in vivo dosimetry.

The alpha-emitter astatine-211 (T(1/2) = 7.2 h) has great potential for use in targeted radionuclide therapy. Its potent alpha-radiation makes (211)At unsuitable for dose planning. Its x-rays can be used for gamma-camera monitoring of the radioactivity distribution during therapy but not for accurate estimation of absorbed dose in critical organs. This study was intended to establish whether the absorbed dose delivered by astatinated antibody could be accurately determined by analogue labeling with radiohalogens, better suited for quantitative measurements in vivo. PET facilitates quantitative pharmacokinetics; possible halogen labels are, e.g., (76)Br (T(1/2) = 16.2 h) and (124)I (T(1/2) = 4.18 d). Antibody A33 was labeled with (76)Br, (125)I and (211)At using N-succinimidyl-p-halobenzoates. The conjugates were co-injected into Sprague-Dawley rats. Radioactivity concentrations in different organs and tissues were measured at three time points. Pharmacokinetic data were used to calculate absorbed doses. (125)I and (76)Br reflected the biokinetics of astatine reasonably well. The absorbed doses in bladder, kidney, pancreas, liver, bone and brain were determined with 10% accuracy. The absorbed doses in stomach, spleen and thyroid were underestimated by a factor 2-3. Positron-emitting analogues can be used to predict the astatine-derived dose in critical organs. Correction factors should be used for stomach, spleen and thyroid.

Animals↗

PubMedDate not supplied

Evaluation of ((4-hydroxyphenyl)ethyl)maleimide for site-specific radiobromination of anti-HER2 affibody.

Affibody molecules are a new class of small phage-display selected proteins using a scaffold domain of the bacterial receptor protein A. They can be selected for specific binding to a large variety of protein targets. An affibody molecule binding with high affinity to a tumor antigen HER2 was recently developed for radionuclide diagnostics and therapy in vivo. The use of the positron-emitting nuclide (76)Br (T(1/2) = 16.2 h) could improve the sensitivity of detection of HER2-expressing tumors. A site-specific radiobromination of a cysteine-containing variant of the anti-HER2 affibody, (Z(HER2:4))(2)-Cys, using ((4-hydroxyphenyl)ethyl)maleimide (HPEM), was evaluated in this study. It was found that HPEM can be radiobrominated with an efficiency of 83 +/- 0.4% and thereafter coupled to freshly reduced affibody with a yield of 65.3 +/- 3.9%. A "one-pot" labeling enabled the radiochemical purity of the conjugate to exceed 97%. The label was stable against challenge with large excess of nonlabeled bromide and in a high molar strength solution. In vitro cell tests demonstrated that radiobrominated affibody binds specifically to the HER2-expressing cell-line, SK-OV-3. Biodistribution studies in nude mice bearing SK-OV-3 xenografts have shown tumor accumulation of 4.8 +/- 2.2% IA/g and good tumor-to-normal tissue ratios.

Animals↗

PubMedDate not supplied

Targeting against epidermal growth factor receptors. Cellular processing of astatinated EGF after binding to cultured carcinoma cells.

BACKGROUND: The alpha-emitting nuclide 211At is of great interest for radionuclide therapy when coupled to a tumor-targeting biomolecule, e.g. epidermal growth factor (EGF) the receptors of which are overexpressed in many malignancies. However, almost no information concerning the cellular processing of astatinated targeting agents is available. MATERIALS AND METHODS: We indirectly astatinated EGF ([211At]-benzoate-EGF) and studied its cellular processing in A-431 carcinoma cells in comparison with data concerning [125I]-benzoate-EGF. RESULTS: The biological half-life of astatine (3.5 h) was longer than the half-life of the iodine label (1.5 h). The increase of the half-life was due to longer retention of the internalised astatine radioactivity. The maximum accumulation for the astatine label occurred later (4-6h) than that for the iodine label (2-4h), indicating a slower excretion of astatine that was confirmed in experiment with 211At/1251-benzoate-EGF. CONCLUSION: The long retention of astatine might be advantageous for radionuclide therapy.

Astatine↗

PubMedDate not supplied

Radio-iodination of monoclonal antibody using potassium [125I]-(4-isothiocyanatobenzylammonio)-iodo-decahydro-closo-dodecaborate (iodo-DABI).

BACKGROUND: Negatively-charged polyhedral boron clusters can be easily halogenated with highly stable boron-halogen bonds and are promising in radionuclide diagnostics and cancer therapy. MATERIALS AND METHODS: The radio-iodination conditions for the closo-dodecaborate anion and for the conjugation of its labeled isothiocyanatobenzylammonio derivative to the monoclonal antibody (mAb) were optimized. RESULTS: The labeling yield was about 90% and the overall conjugation yield was 55-60%. The in vitro stability of the radio-iodinated mAb was good under physiological and non-physiological conditions. The immunoreactivity of the labeled mAb (SK-BR-3 cells) was retained in the one-pot two-step labeling. CONCLUSION: Negatively-charged polyhedral boron clusters can be used for indirect radio-iodination of mAbs.

Antibodies, Monoclonal↗