Labeling of vasoactive intestinal peptide (VIP) and VIP 10-28 fragment with radioiodine by direct method. Comparative study of the kinetics biodistribution and affinity for neuroendocrine tumor cells

In the progress of the Nuclear Medicine, many protein based radiopharmaceuticals have been developed in the last years using antibodies and, more recently, biologically active natural peptides or similar synthetic peptides. In the search for agents with specificity for the target tissue in tumors detection, it was verified that small sequences of amino acids may interact with selective sites, with homogenous distribution, fast accumulation in tissues and fast blood clearance when compared to the antibodies. Among the peptides used in the diagnosis of tumors, Vasoactive Intestinal Peptide (VIP) has been studied. VIP labeled with iodine-123 is applied in the images of intestinal adenocarcinoma and endocrine tumors. The molecule of VIP contains two tyrosine residues, in the positions 10 and 22 that are, theoretically, equally susceptible to radioiodination for direct method. The objective of this work was to produce VIP labeled with radioiodine (iodine-123), in order to introduce to the brazilian medical class this radiopharmaceutical of interest for the diagnosis and recurrence of tumors that express specific receptors. In an unpublished way, the work studied the labeling and the kinetic distribution of the VIP fragment (VIP 10-28) and verified its potential as radiopharmaceutical applied in the identification of tumors that express VIP receptors. After the choice of the appropriated technique for labeling VIP and VIP 10-28 with radioiodine, using Ceremonial T as oxidant agent and sodium metabisulfite as reducing agent, the quality control procedures were accomplished (electrophoresis and high performance liquid chromatography, HPLC) for radiochemical purity determination as well as the separation of the radiochemical species obtained. Labeling and quality control procedures applied were efficient and accurate. [131I]VIP and [131l]VIP 10-28 were obtained with high radiochemical purity (> 95%). The purification studies to remove free radioiodine in the labeling mixture (simple purification) and to produce the radiopharmaceutical with high specific activity (complex purification and HPLC), were both efficient in the separation of the species in the reaction mixtures, as demonstrated by quality control procedures. Biological distribution studies were accomplished by venous administration of the radiopharmaceuticals in laboratory animals: biodistribution study of [131I]VIP and [131I]VIP 10-28 in normal Swiss mice, [131I]VIP not purified and purified in Swiss mice with tumor and [131I]VIP and [131I]VIP 10-28 in Nude mice with tumor, scintigraphic images of [131/123I]VIP and [123I]VIP 10-28 in Swiss and Nude mice and Wistar rats with tumor. In vitro studies were accomplished to determine the percentage of [131I]VIP and [131I]VIP 10-28 bound to plasmatic proteins, stability study of [131I]VIP and [131I]VIP 10-28 in human plasma and the affinity and internalization of [131I]VIP and [131I]VIP 10-28 by tumour adenocarcinoma cells of human rectal colon (HT-29). All biological distribution studies demonstrated that both [131/123I]VIP and [131/123I]VIP 10-28 showed fast blood clearance, low renal and liver uptake, relative uptake in thyroid, showing in vivo dehalogenation and good uptake in tumour. Comparative biological distribution of the radiopharmaceuticals showed high uptake in the stomach for both peptides. The blood clearance of the fragment was slower, and influences the visualization of the tumour mass. The radiopharmaceuticals, [123I]VIP and [123I]VIP 10-28, were obtained with high radiochemical purity, but with low radiochemical yield when comparing with labeling procedures using iodine-131. Quality control assays of [123I]Na indicated that the presence of radiochemical and radionuclide impurities influenced on labeling results. (author)