Biological studies in animal models using [99m Tc](CO)3 recombinant annexin V as diagnostic agent of apoptotic processes

• Published in: Nuclear medicine and biology Vol. 38; no. 2; pp. 279 - 285
• Main Authors: Terán, Mariella Adriana, Martínez, Elena, Reyes, Ana L, Paolino, Andrea, Vital, Marcelo, Esperón, Patricia, Pacheco, Jose P, Savio, Eduardo
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-02-2011; Elsevier
• Subjects: Animals; Annexin; Annexin A5 - chemistry; Annexin A5 - pharmacokinetics; Apoptosis; Biodistributions; Biological and medical sciences; Chemical Phenomena; Contrast media. Radiopharmaceuticals; Drug Stability; Female; Humans; Medical sciences; Models, Animal; Organotechnetium Compounds; Pharmacology. Drug treatments; Radiology; Rats; Rats, Wistar; Recombinant Proteins - chemistry; Recombinant Proteins - pharmacokinetics; Scintigraphic images; Tricarbonyl; Tricarbonyl; Biodistributions; Scintigraphic images; Annexin; Apoptosis; Radionuclide study; Nuclear medicine; Scintigraphy; Technetium Carbonyl Complexes; Diagnostic agent; Animal; Technetium 99mTc; Distribution; Medical imagery; Recombinant protein; Pharmacokinetics; Radioisotopic product; Biomedical engineering
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2010.08.007

Abstract Introduction There are many diseases associated with variations in the expression of apoptosis such as organ rejection after transplantation, myocardial ischemia or infarct and neurodegenerative diseases. For this reason, the early visualization of this process is relevant to set fast and effective therapeutic strategies. Methods The precursor was prepared according to the procedure reported by R. Alberto, R. Schibli, P. Schubiger, U. Abram, and T. Kaden [Reactions with the technetium and rhenium carbonyl complexes (NEt4 )[MX 3CO 3 ]. Synthesis and structure of Tc(CN-But) 3CO 3 ](NO3 ) and (Net4 )[Tc2 (μ-SCH2 CH2 OH) 3CO 3 ], Polyhedron 1996;15: 1079–89]. Recombinant annexin V was incubated with [99m Tc](H2 O)3(CO)3+ solution, previously neutralized with buffer. Biodistribution studies were performed in 8-week-old female Wistar rats. Animals were housed and treated in compliance with institutional guidelines related to animal experimentation. Work protocol was previously approved by the Animal Ethics Committee of the university. Two groups of rats were defined. One was used as control and the other group was previously injected with 150 mg/kg ip of cyclophosphamide to induce apoptosis. Results The synthesis of carbonyl precursor achieved yields higher than 90%, and the radiolabeled protein was obtained with 92% of radiochemical purity and high stability in vitro. An important uptake in apoptotic tissues was confirmed by biodistributions, scintigraphic images and histological studies. Conclusions Biodistribution studies revealed hepatobiliary elimination, high stability in vivo and important uptake in the reticuloendothelial system. In the pathologic model, higher uptake values correspond to the liver, spleen, lungs and femur. Histological studies confirmed the development of apoptosis at 8 and 24 h postinduction in the spleen and lymphocyte bulks in the peribronchial area. Scintigraphic images confirmed high uptake both the spleen and the lungs.