Indium-111-DOTA-lanreotide: biodistribution, safety and radiation absorbed dose in tumor patients.

Abstract

UNLABELLED:

Imaging with radiolabeled somatostatin/vasoactive intestinal peptide analogs 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 biodistribution, safety and radiation absorbed dose of 111In-1,4,7,10-tetraazacyclododecane-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 111In-DOTA-lanreotide was initially investigated in 10 patients (3 lymphomas, 5 carcinoids and 2 intestinal adenocarcinomas). Indium-111 -DOTA-lanreotide was then administered to 14 cancer patients evaluated for possible radiotherapy with 90Y-DOTA-lanreotide (8 neuroendocrine tumors, 4 intestinal adenocarcinomas, 1 Hodgkin lymphoma and 1 prostate cancer). After intravenous administration of 111In-DOTA-lanreotide (approximately = 150 MBq; 10 nmol/patient), sequential images over one-known tumor site were recorded during the initial 30 min after peptide application. Thereafter, whole-body images were acquired in anterior and posterior views up to 72 hr postinjection. Dosimetry calculations were performed on the basis of scintigraphic data, urine, feces and blood activities. A comparison with 111In-DTPA-D-Phe1-octreotide (111In-OCT) scintigraphy was performed in 8 of the patients.

RESULTS:

After an initial rapid blood clearance [results of biexponential fits: T(eff1) 0.4 min (fraction a1 80%) and T(eff2) 13 min (fraction a2 14%)], the radioactivity was excreted into the urine and amounted to 42% +/- 3% of the injected dose (%ID) within 24 hr and 62% +/- 6%ID within 72 hr after injection of 111In-DOTA-lanreotide. In all patients, tumor sites were visualized during the initial minutes after injection of 111In-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 111In-DOTA-lanreotide in the tumors were T(eff1) 4.9 +/- 2.2 and T(eff2) 37.6 +/- 6.6 hr, and the mean residence time tau 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 effects were noted after 111In-DOTA-lanreotide application. The 111In-DOTA-lanreotide radiation absorbed tumor dose was significantly higher (ratio 2.25 +/- 0.60, p < 0.01) when directly compared with 111In-OCT.

CONCLUSION:

Indium-111 -DOTA-lanreotide shows a high tumor uptake for a variety of different human tumor types, has a favorable dosimetry over 111In-OCT and is clinically safe.

• Authors: I Virgolini, I Szilvasi, A Kurtaran, P Angelberger, M Raderer, E Havlik, F Vorbeck, C Bischof, M Leimer, G Dorner, K Kletter, B Niederle, W Scheithauer, P Smith-Jones
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 39 Issue 11 Pg. 1928-36 (Nov 1998) ISSN: 0161-5505 [Print] United States
• PMID: 9829585 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indium Radioisotopes
• Peptides, Cyclic
• lanreotide
• Somatostatin
• Octreotide

Topics

• Adenocarcinoma (diagnostic imaging)
• Adult
• Aged
• Carcinoid Tumor (diagnostic imaging)
• Female
• Half-Life
• Humans
• Indium Radioisotopes (pharmacokinetics)
• Lymphoma (diagnostic imaging)
• Male
• Middle Aged
• Neuroendocrine Tumors (diagnostic imaging)
• Octreotide (pharmacokinetics)
• Peptides, Cyclic (pharmacokinetics)
• Radiometry
• Somatostatin (analogs & derivatives, pharmacokinetics)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon