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


CONCLUSIONS
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.
Virgolini
I
I
Department of Nuclear Medicine, Ludwig Boltzmann Institute for Nuclear Medicine, University of Vienna, Austria.
Szilvasi
I
I
Kurtaran
A
A
Angelberger
P
P
Raderer
M
M
Havlik
E
E
Vorbeck
F
F
Bischof
C
C
Leimer
M
M
Dorner
G
G
Kletter
K
K
Niederle
B
B
Scheithauer
W
W
Smith-Jones
P
P
D000230:Adenocarcinoma / Q000000981:diagnostic imaging; D000328:Adult; D000368:Aged; D002276:Carcinoid Tumor / Q000000981:diagnostic imaging; D005260:Female; D006207:Half-Life; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D008223:Lymphoma / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging; D015282:Octreotide / Q000493:pharmacokinetics; D010456:Peptides, Cyclic / Q000493:pharmacokinetics*; D011874:Radiometry; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D007205:Indium Radioisotopes; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D015282:Octreotide