ABSTRACT
This work analysed the influence of the chelating group and radioligand on somatostatin analogues in vivo and in vitro properties. The presence of DOTA in the radioiodinated peptide produced a labeled analogue with similar blood kinetics and biodistribution to (177)Lu-DOTATATE and with lower abdominal uptake than (131)I-TATE. In addition, (131)I-DOTATATE showed significative tumour uptake, despite not so persistent after 24h. (131)I-DOTATATE can represent a cost-effective alternative to lutetium labeled peptide for neuroendocrine tumours therapy.
Subject(s)
Iodine Radioisotopes , Lutetium , Neuroendocrine Tumors/diagnostic imaging , Radioisotopes , Somatostatin/analogs & derivatives , Animals , Chelating Agents , Heterocyclic Compounds, 1-Ring , Mice , Neuroendocrine Tumors/radiotherapy , Pharmacokinetics , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Somatostatin/pharmacokinetics , Tissue DistributionABSTRACT
The preparation of N-succinimidyl-4-[131I]iodobenzoate (SIB) has been optimized using an alternative technique employing Cu(I)-assisted radioiododebromination that produces p-[131I]iodobenzoic acid. The reaction conditions were optimized and radiochemical purity of more than 90% was obtained when using 160 degrees C, 60 min reaction time and a [CuCl]/[p-bromobenzoic acid] relation of about 10(-2). After purification, the p-[131I]iodobenzoic acid reacted with TSTU to produce the SIB in a radiochemical yield greater than 98%. Protein conjugation using SIB resulted in a relatively low radiochemical yield. Biological distribution studies evidenced the in vivo stability of the labeled protein.
Subject(s)
Iodine Radioisotopes/chemistry , Iodobenzoates/chemical synthesis , Isotope Labeling/methods , Proteins/chemical synthesis , Radiopharmaceuticals/chemical synthesis , Chromatography, High Pressure Liquid/methods , Iodine Radioisotopes/isolation & purification , Iodobenzoates/chemistry , Iodobenzoates/isolation & purification , Ligands , Proteins/chemistry , Proteins/isolation & purification , Quality Control , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/isolation & purification , TemperatureABSTRACT
Radiolabelled peptides can provide new approaches for radiopharmaceutical development. Several prosthetic groups have been developed for radioiodination of proteins in order to minimize in vivo dehalogenation. In this work, the prosthetic group N-succinimidyl 4-[131I]iodobenzoate ([131I]SIB) was obtained by an alternative procedure that employs Cu(I) assisted radioiododebromination to produce p-[131I]iodobenzoic acid with a radiochemical yield of 92.73 +/- 1.51% (N = 6), followed by the reaction with TSTU (O-(N-succinimidyl)-N,N,N'N'-tetramethyluronium) in alkaline medium. The HPLC profile of the final product, revealed that [131I]SIB was obtained with a radiochemical purity of 98.19 +/- 1.14% (N = 6 Swiss mices (normal group) and animals with inflammation focus developed on the right thigh by tupertine injection) were injected with human immunoglobulin (IgG) radioiodinated with [131I]SIB and by direct method (Iodogen). The comparison of results showed a fast blood clearance, better target organ/background relation and low uptake in thyroid and stomach (p < 0.01) for the protein labelled with [131I]SIB, what suggests a greater in vivo stability.
