D-LYSINE REDUCTION OF IN-111 OCTREOTIDE AND Y-90 OCTREOTIDE RENAL UPTAKE

Indium-111-DTPA-octreotide (In-111-DTPAOC) is used successfully for im aging somatostatin receptor-positive lesions. A new and promising appl ication is its use in peptide-receptor radionuclide therapy (PRRT). Fo r the latter purpose, [DOTA(0),D-Phe(1),Tyr(3)]octreotide (DOTATOC), w hich is suitable for stable radiolabeling with Y-90, is probably even more promising. Significant renal uptake of these octreotide analogs e xists, however, reducing the scintigraphic sensitivity for detection o f small tumors in the perirenal region and limiting the possibilities for PRRT. We showed that the renal uptake of In-111-DTPAOC could be re duced to about 50% of control by L-lysine administration in vivo in ra ts. This study compares the effects of several doses and different met hods of administration of D-and L-lysine, in addition to time-related effects of D-lysine, on kidney uptake of In-111-DTPAOC and Y-90-DOTATO C. Methods: Male Wistar rats (20-250 g) were given In-111-DTPAOC (0.2 MBq, 0.5 mu g-0.5 mg intravenously, intraperitoneally or orally) in th e presence or absence of D- or L-lysine. At 1, 4 or 24 hr, the rats we re killed, and the organs were isolated and counted for radioactivity. In different experiments, male Wistar rats (200-250 g) were given Y-9 0-DOTATOC (1 MBq, 0.5 mu g intravenously) in the presence or absence o f D-lysine. At 24 hr, the rats were killed, and the organs were isolat ed and counted for radioactivity. Results: Administration of D- or L-l ysine in a single intravenous dose of 400 mg/kg, resulted in more than 50% inhibition of kidney uptake of In-111-DTPAOC at all time points t ested, independently of the mass of In-111-DTPAOC used. Higher or repe ated doses of lysine did not give a significantly higher percentage in hibition. D-lysine, given orally in a dose of 400 mg/kg at 30 or 15 mi n before In-111-DTPAOC injection, resulted in 30% and 20% inhibition o f kidney uptake, respectively. L-lysine, given orally 30 min before In -111-DTPAOC administration, resulted in 30% inhibition as well. Inhibi tion of kidney uptake of In-111-DTPAOC by L-lysine after intraperitone al administration was 40%. After L-lysine administration, In-111-DTPAO C was decreased in the kidneys and in somatostatin receptor-positive o rgans such as the pancreas and adrenal glands. In contrast, D-lysine d id not have a significant effect on uptake in octreotide receptor-posi tive organs. Renal uptake of Y-90-DOTATOC was reduced by 65% by intrav enous D-lysine, whereas radioactivity in blood, pancreas and adrenal g lands was not affected. Conclusion: D-lysine may be preferred to L-lys ine for reduction of renal uptake of radioactivity during scintigraphy and PRRT because of its lower toxicity and because it should not inte rfere with the natural amino acid metabolic balance.