Publication

Diagnostic versus therapeutic doses of [(177)Lu-DOTA-Tyr(3)]-octreotate: uptake and dosimetry in somatostatin receptor-positive tumors and normal organs

Journal Paper/Review - Feb 1, 2007

Units
PubMed
Doi

Citation
Müller C, Forrer F, Bernard B, Melis M, Konijnenberg M, Krenning E, de Jong M. Diagnostic versus therapeutic doses of [(177)Lu-DOTA-Tyr(3)]-octreotate: uptake and dosimetry in somatostatin receptor-positive tumors and normal organs. Cancer Biother Radiopharm 2007; 22:151-9.
Type
Journal Paper/Review (English)
Journal
Cancer Biother Radiopharm 2007; 22
Publication Date
Feb 1, 2007
Issn Print
1084-9785
Pages
151-9
Brief description/objective

AIM
The aim of this study was to investigate the influence of a diagnostic versus therapeutic dose of [(177)Lu-DOTA-Tyr(3)]octreotate on the uptake, effects, and dosimetry in somatostatin receptor subtype 2(sst2)-positive tumors and normal organs in a rat tumor model.

MATERIALS AND METHODS
Lewis rats bearing rat pancreatic CA20948-tumor grafts were injected intravenously with different amounts of radioactivity and peptide of [(177)Lu-DOTA-Tyr(3)]octreotate: 3 MBq/0.5 microg (group A), 3 MBq/15 microg (group B), 300 MBq/15 microg (group C), and 555 MBq/15 microg (group D). Biodistribution studies were performed at several time points between 3 and 13 days post injection. Ex vivo and in vitro autoradiography was performed with frozen tumor sections.

RESULTS
Normal sst2-positive tissues showed a significantly higher uptake of radioactivity [%IA/g] when a low peptide amount was injected. On the other hand, the radioactivity concentration [%IA/g] in sst2-negative tissues and organs (blood, muscles, kidney, and liver) were comparable (groups A and B), independent of the injected peptide amount. Initially, this held true for the tumors as well. Yet, over time, we found a decrease in the radioactivity concentration in the tumors of groups A and B, because of tumor growth. On the other hand, therapeutic amounts of radioactivity (groups C and D) resulted in a significant reduction of tumor size, where radioactivity concentration remained higher than in groups A and B, despite the use of the high peptide amounts. Ex vivo autoradiograms of tumor sections confirmed these results. In vitro autoradiography performed on adjacent tumor sections revealed a reduced density of sst2 in tumors from animals that received a therapeutic radioactivity dose. Ki67-antibody immunohistochemistry showed an absence of proliferating tumor cells after therapy.

CONCLUSIONS
The differences in radioactivity retention in tumors after diagnostic or therapeutic doses, depending on a change in tumor kinetics, have to be taken into account when calculating tumor-absorbed radiation doses.