Up-regulation of somatostatin receptor density on rat CA20948 tumors escaped from low dose [(177)Lu-DOTA(0),Tyr(3)]octreotate therapy

Melis, M; Forrer, F; Capello, A; Bijster, M; Bernard, B F; Reubi, J C; Krenning, E P; De Jong, M (2007). Up-regulation of somatostatin receptor density on rat CA20948 tumors escaped from low dose [(177)Lu-DOTA(0),Tyr(3)]octreotate therapy. Quarterly journal of nuclear medicine and molecular imaging, 51(4), pp. 324-33. Torino: Minerva Medica

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AIM: Peptide receptor radionuclide therapy using the somatostatin analogue [(177)Lu-DOTA(0),Tyr(3)]octreotate is a convincing treatment modality for metastasized neuroendocrine tumors. Therapeutic doses are administered in 4 cycles with 6-10 week intervals. A high somatostatin receptor density on tumor cells is a prerequisite at every administration to enable effective therapy. In this study, the density of the somatostatin receptor subtype 2 (sst2) was investigated in the rat CA20948 pancreatic tumor model after low dose [(177)Lu-DOTA(0), Tyr(3)]octreotate administration resulting in approximately 20 Gy tumor radiation absorbed dose, whereas 60 Gy is needed to induce complete tumor regression in these and the majority of tumors. METHODS: Sixteen days after inoculation of the CA20948 tumor, male Lewis rats were injected with 185 MBq [(177)Lu-DOTA(0),Tyr(3)]octreotate to initiate a decline in tumor size. Approximately 40 days after injection, tumors re-grew progressively after initial response. Quantification of sst2 expression was performed using in vitro autoradiography on frozen sections of three groups: control (not-treated) tumors, tumors in regression and tumors in re-growth. Histology and proliferation were determined using HE- and anti-Ki-67-staining. RESULTS: The sst2 expression on CA20948 tumor cells decreased significantly after therapy to 5% of control level. However, tumors escaping from therapy showed an up-regulated sst2 level of 2-5 times higher sst2 density compared to control tumors. CONCLUSION: After a suboptimal therapeutic dose of [(177)Lu-DOTA(0),Tyr(3)]octreotate, escape of tumors is likely to occur. Since these cells show an up-regulated sst2 receptor density, a next therapeutic administration of radiolabelled sst2 analogue can be expected to be highly effective.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute of Pathology
UniBE Contributor:	Reubi-Kattenbusch, Jean-Claude
Subjects:	500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health
ISSN:	1824-4661
ISBN:	17923824
Publisher:	Minerva Medica
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:54
Last Modified:	05 Dec 2022 14:16
PubMed ID:	17923824
Web of Science ID:	000252467900007
URI:	https://boris.unibe.ch/id/eprint/22758 (FactScience: 36469)