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Inhomogeneous activity distribution of (177)Lu-DOTA (0)-Tyr (3)-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice.

Journal article
Authors Jenny Oddstig
Peter Bernhardt
Helena Lizana
Ola Nilsson
Håkan Ahlman
Lars Kölby
Eva Forssell-Aronsson
Published in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
Volume 33
Issue 1
Pages 229-239
ISSN 1423-0380
Publication year 2012
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Biomedicine, Department of Pathology
Institute of Clinical Sciences, Department of Plastic Surgery
Institute of Clinical Sciences
Pages 229-239
Language en
Links dx.doi.org/10.1007/s13277-011-0268-...
Subject categories Radiological physics

Abstract

The aim of this study was to investigate the activity distribution in neouroendocrine tumors after diagnostic, or therapeutic, amounts of [(177)Lu-DOTA(0)-Tyr(3)]-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 (177)Lu-octreotate. At different time points thereafter (4 h to 13 days), a second injection of [(111)In-DOTA(0)-Tyr(3)]-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 (177)Lu, 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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