Inhomogeneous activity distribution of 177Lu-DOTA0-Tyr3-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice | springermedicine.com

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01-02-2012 | Research Article

Inhomogeneous activity distribution of ¹⁷⁷Lu-DOTA⁰-Tyr³-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice

Authors: Jenny Oddstig, Peter Bernhardt, Helena Lizana, Ola Nilsson, Håkan Ahlman, Lars Kölby, Eva Forssell-Aronsson

Published in: Tumor Biology | Issue 1/2012

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Abstract

The aim of this study was to investigate the activity distribution in neouroendocrine tumors after diagnostic, or therapeutic, amounts of [¹⁷⁷Lu-DOTA⁰-Tyr³]-octreotate and to investigate how the activity distribution influences the absorbed dose. Furthermore, the activity distribution of a second administration of radiolabeled octreotate was studied. Nude mice with subcutaneously grown human midgut carcinoid (GOT1) were injected intravenously with different amounts of ¹⁷⁷Lu-octreotate. At different time points thereafter (4 h to 13 days), a second injection of [¹¹¹In-DOTA⁰-Tyr³]-octreotate was given to estimate the somatostatin receptor (sstr) expression. The activity distribution in the tumors was then determined. Monte Carlo simulations with PENELOPE were performed for dosimetry. Fifty-one out of 58 investigated tumors showed a lower activity concentration in the peripheral part than in the central part of the tumor. The amount of activity injected, or time after administration, did neither influence the relative activity nor the sstr distribution in the tumor. After an initial down-regulation (at 4–24 h), there was an up-regulation of sstr (1.5–2 times, at 7–14 days). Monte Carlo simulations demonstrated an inhomogeneous absorbed dose distribution in the tumor using ¹⁷⁷Lu, with twice as high absorbed dose centrally than peripherally. The high activity concentration centrally and the up-regulation of sstr demonstrated will facilitate fractionated therapy using radiolabeled somatostatin analogues if similar results will be obtained also in patients. The inhomogeneous activity distribution in the tumor has to be taken into account when the absorbed dose distribution in tumor is calculated.

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Title: Inhomogeneous activity distribution of 177Lu-DOTA0-Tyr3-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice
Authors: Jenny Oddstig
Peter Bernhardt
Helena Lizana
Ola Nilsson
Håkan Ahlman
Lars Kölby
Eva Forssell-Aronsson
Publication date: 01-02-2012
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 1/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-011-0268-0

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