Studies on radiolabeled somatostatin analogues in rats and in patients.

We present the pharmacokinetical aspects of somatostatin receptor scintigraphy in rats with the radioiodinated [Tyr3]octreotide and 111In-labeled [DTPA-D-Phe1]octreotide. The residence time of both radionuclides in somatostatin receptor-positive tissues and tumors is completely different, indicating the difference in metabolism of the two radiopharmaceuticals. The effects of the injected radioactive dose and mass of the radioligand and its injection rate on the biodistribution is intensively studied. We found in rat that the uptake of radioactivity in somatostatin receptor-positive tissues is a bell-shaped function of the injected mass depending on the tissue under study, being optimal between 0.5-5 micrograms. This indicates that the sensitivity of the detection of somatostatin receptor-positive tumor by receptor scintigraphy may be improved by varying the mass of the radiopharmaceutical, which has also been confirmed in patient studies. Priming with somatostatin analogues at various time points relative to the radioligand was studied as well. In all the somatostatin receptor-positive tissues we found a significant change in % injected dose uptake of radioactivity, depending on the ligand, its mass and the tissue under study. This might also be a means to increase the target to background ratio in somatostatin receptor scintigraphy. The possible role of the radiopharmaceutical [111In-DTPA-D-Phe1]RC-160 in somatostatin scintigraphy in visualizing somatostatin receptor-positive tumors that do not bind octreotide, for instance somatostatin receptor subtype 4, is discussed. Internalization of the receptor-ligand and metabolism of the radioiodinated and 111In-labeled somatostatin analogues were studied in vitro and in vivo to get insight into metabolism of the radioligand. Internalization of the radioligand is of special importance when radiotherapy of certain somatostatin receptor-positive human tumors with alpha- or beta-emitting radiolabeled somatostatin analogues is considered. Further, peptide receptor radionuclide therapy with several radionuclides is reviewed.