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THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
Rivista di Medicina Nucleare e Imaging Molecolare
A Journal on Nuclear Medicine and Molecular Imaging
Affiliated to the and to the International Research Group of Immunoscintigraphy
Indexed/Abstracted in: Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index (SciSearch), Scopus
Impact Factor 2,413
ENDOCRINOLOGY - II
The Quarterly Journal of Nuclear Medicine 1999 December;43(4):356-66
Therapy of neuroendocrine tumors with radiolabeled somatostatin-analogues
De Jong M., Breeman W. A. P., Bernard H. F., Kooij P. P. M., Slooter G. D.*, Van Eijck C. H. J.*, Kwekkeboom D. J., Valkema R., Macke H. R.**, Krenning E. P.**
From the Department of Nuclear Medicine *Surgery, **Kantonspital Basel, Switzerland and ***Internal Medicine III University Hospital and Erasmus University Rotterdam, The Netherlands
Peptide receptor scintigraphy with the radioactive somatostatin-analogue [111In-DTPA0]octreotide (DTPA = diethylenetriaminepentaacetic acid) is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumors. With this technique primary tumors and metastases of neuroendocrine cancers as well as of many other cancer types can be localised. A new application is the use of peptide receptor radionuclide therapy, administrating high doses of 111In- or 90Y-labeled octreotide-analogues.
Preclinical. We investigated the radiotherapeutic effect of 90Y- and 111In-labeled [DOTA0,Tyr3]octreotide (DOTA= tetraazacyclododecanetetraacetic acid) or [111In-DTPA0]octreotide in Lewis rats bearing the somatostatin receptor-positive rat pancreatic tumor CA20948 in A) the flank or B) in the liver.
Patients. Thirty end-stage patients with mostly neuroendocrine progressing tumors were treated with [111In-DTPA0]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase 1 trial.
Preclinical results. A) Flank model: at least two 111MBq injections of [111In-DOTA0,Tyr3]octreotide were needed to reach tumor response, in 40% of the animals complete tumor remission was found after a follow-up period of 10 months. One or two injections of [90Y-DOTA0,Tyr3] octreotide yielded transient stable disease.
B) Liver model: we found that peptide receptor radionuclide therapy is only effective if somatostatin receptors are present on the tumors, and is therefore receptor-mediated. High radioactive doses of 370 MBq [111In-DTPA0]octreotide or 93 MBq [90Y-DOTA0,Tyr3]octreotide can inhibit the growth of somatostatin receptor-positive metastases.
Clinical results. There were no major clinical side effects after up to 2 years treatment, except that a transient decline in platelet counts and lymphocyte subsets can occur. Promising beneficial effects on clinical symptoms, hormone production and tumor proliferation were found. Of the 21 patients with progressive disease at baseline and who received a cumulative dose of more than 20 GBq [111In-DTPA0]octreotide, 8 patients showed stabilisation of disease and 6 other patients a reduction in size of tumors. There is a tendency towards better results in patients whose tumors have a higher accumulation of the radioligand.
Conclusion. Radionuclide therapy with octreotide-derivatives is feasible, both with 111In and 90Y as radionuclides.