INDIUM-111-DOTA-LANREOTIDE - BIODISTRIBUTION, SAFETY AND RADIATION ABSORBED DOSE IN TUMOR PATIENTS

Imaging with radiolabeled somatostatin/vasoactive intestinal peptide a nalogs has recently been established for the localization diagnosis of a variety of human tumors including neuroendocrine tumors, intestinal adenocarcinomas and lymphomas. This study reports on the biodistribut ion, safety and radiation absorbed dose of In-111-1,4,7,10-tetraazacyc lododecane-N,N',N '',N'''-tetraacetic acid (DOTA)-lanreotide, a novel peptide tracer, which identifies hSST receptor (R) subtypes 2 through 5 with high affinity, and hSSTR1 with low affinity. Methods: The tumor localizing capacity of In-111-DOTA-lanreotide was initially investiga ted in 10 patients (3 lymphomas, 5 carcinoids and 2 intestinal adenoca rcinomas). Indium-111-DOTA-lanreotide was then administered to 14 canc er patients evaluated for possible radiotherapy with Y-90-DOTA-lanreot ide (8 neuroendocrine tumors, 4 intestinal adenocarcinomas, 1 Hodgkin lymphoma and 1 prostate cancer). After intravenous administration of I n-111-DOTA-lanreotide congruent to 150 MBq; 10 nmol/patient), sequenti al images over one-known tumor site were recorded during the initial 3 0 min after peptide application. Thereafter, whole-body images were ac quired in anterior and posterior views up to 72 hr postinjection. Dosi metry calculations were performed on the basis of scintigraphic data, urine, feces and blood activities. A comparison with In-111-DTPA-D-Phe (1)-octreotide (In-111-OCT) scintigraphy was performed in 8 of the pat ients. Results: After an initial rapid blood clearance [results of bie xponential fits: T-eff1 0.4 min (fraction a(1) 80%) and T-eff2 13 min (fraction a(2) 14%)], the radioactivity was excreted into the urine an d amounted to 42% +/- 3% of the injected dose (%ID) within 24 hr and 6 2% +/- 6%ID within 72 hr after injection of In-111-DOTA-lanreotide. in all patients, tumor sites were visualized during the initial minutes after injection of In-111-DOTA-lanreotide. The mean radiation absorbed dose amounted to 1.2 (range 0.21-5.8) mGy/MBq for primary tumors and/ or metastases. The effective half-lives of In-111-DOTA-lanreotide in t he tumors were T-eff1 4.9 +/- 2.2 and T-eff2 37.6 +/- 6.6 hr, and the mean residence time 7 was 1.8 hr. The highest radiation absorbed doses were calculated for the spleen (0.39 +/- 0.13 mGy/MBq), kidneys (0.34 +/- 0.08 mGy/MBq), urinary bladder (0.21 +/- 0.03 mGy/MBq) and liver (0.16 +/- 0.04 mGy/MBq). The effective dose was 0.11 +/- 0.01 (range 0 .09-0.12) mSv/MBq. During the observation period of 72 hr, no side eff ects were noted after In-111-DOTA-lanreotide application. The In-111-D OTA-lanreotide radiation absorbed tumor dose was significantly higher (ratio 2.25 +/- 0.60, p < 0.01) when directly compared with In-111-OCT . Conclusion: Indium-111-DOTA-lanreotide shows a high tumor uptake for a variety of different human tumor types, has a favorable dosimetry o ver In-111-OCT and is clinically safe.