EVALUATION IN-VITRO AND IN RATS OF TB-161-DTPA-OCTREOTIDE, A SOMATOSTATIN ANALOG WITH POTENTIAL FOR INTRAOPERATIVE SCANNING AND RADIOTHERAPY

The characteristics of terbium-161 diethylene triamine penta-acetic acid (DTPA) labelled octreotide with respect to specific binding to somatostatin (octreotide) receptors on rat brain cortex membranes, biological activity, uptake and excretion by isolated perfused rat livers and metabolism in vivo in normal and tumour-bearing rats were determined and compared to those of indium-111 DTPA-octreotide. The results of the binding studies demonstrate that Tb-161-DTPA-octreotide is a high-affinity radioligand for somatostatin receptors, with an affinity comparable to that of In-111-DTPA-octreotide. Rat growth hormone secretion inhibition experiments showed that Tb-161-DTPA-octreotide has a similar potency to In-111-DTPA-octreotide. Tb-161-DTPA-octreotide appeared to be taken up even less by the isolated perfused rat liver than In-111-DTPA-octreotide, as almost no tracer disappeared from the perfusion medium. Furthermore, hardly any radioactivity was found in the liver, and excretion into the bile was negligible. The biodistribution studies showed that for octreotide receptor-positive organs, such as pancreas and adrenals, uptake of Tb-161-DTPA-octreotide is lower then that of In-111-DTPA-octreotide. However, as the clearance from the blood of the former compound is faster than that of the latter, the tissue/blood ratio is higher in the case of Tb-161-DTPA-octreotide than with In-111-DTPA-octreotide. Furthermore, these studies demonstrated that the uptake of Tb-161-DTPA-octreotide by the renal tubular cells after glomerular filtration can be reduced by administration of lysine or sodium maleate. Increase in urine production before and during the experiment had no effect on the kidney uptake of Tb-161-DTPA-octreotide. Finally, it appeared that a maximal Labelling efficiency of Tb-161-DTPA-octreotide is essential, as with decreasing efficiency the uptake in the octreotide receptor-positive organs decreased, whereas non-specific uptake in the other organs was increased. It is concluded that, on the basis of the favourable physical characteristics of Tb-161 combined with the in vitro and in vivo studies performed with Tb-161-DTPA-octreotide, the latter is a promising radiopharmaceutical for both intraoperative scanning and radiotherapy. Studies in patients need to be performed now to see whether Tb-161-DTPA-octreotide can indeed open new therapeutic applications for patients bearing octreotide receptor-positive tumours.