Iodine-131 labelled octreotide: Not an option for somatostatin receptor therapy

Gamma-emitting radiopeptides are useful for scintigraphy of tumours on the basis of receptor binding. Likewise, beta-emitting radiopeptides may be used in radionuclide therapy of such tumours. As iodine-131 suggested to be suitable for this purpose, experiments were performed using three somatostatin analogues, in which the effects of coupling of a therapeutic dose of I-131 to such peptides were investigated. This study deals with the radioiodination of very small amounts of peptide on a therapeutic scale, the required purification procedures after radioiodination, and the influence of high beta fluxes from I-131 On a peptide during radioiodination and purification. Based on the regularly used therapeutic doses of I-131 in cancer treatment and our previous experience with [In-111-DTPA-D-Phe(1)]-octreotide, it was assumed that a minimal effective therapeutic dose of 3.7 GBq I-131 has to be coupled to a maximum of approximate to 100 mu g peptide, representing only a slight excess of peptide over I-131. This contrasts with non-peptide radiopharmaceuticals in which high compound to radionuclide ratios are usually used. Labelling at low peptide to radionuclide ratios (low labelling yields) results in the formation of di-iodinated compounds, whereas at high peptide to radionuclide ratios (high labelling yields) mono-iodinated products of low specific activity are formed. Thus, after radioiodination the desired mono-iodinated peptide has to be separated from unreacted iodide, and from di-iodinated and unreacted peptide, as both compounds compete for the receptors. Possible radiolysis of the peptide during labelling and separation steps were investigated by irradiating 30 mu g unlabelled peptide with 370 MBq I-131 in a small volume. The peptide composition of the incubation mixtures was investigated by high-performance liquid chromatography after irradiation for 30 min to 24 h, The results showed that the peptide was degraded with a half-life of less than 1 h, During the preparation of a real therapeutic dose (at much higher beta-flux) the peptide will be degraded even faster during the various steps required. In conclusion, intact mono-iodinated I-131-labelled somatostatin analogues for peptide receptor therapy will be difficult to obtain.