First proof in patients of an improved "magic bullet" for cancer detection and radio-therapy

September 12, 2011

First proof in patients of an improved “magic bullet” for cancer detection and radio-therapy

Salk Institute scientists collaborate with scientists of the University of Bern and physicians from the University Hospital of Freiburg (D) on the discovery and clinical testing of agents that "detect" more metastatic neuroendocrine tumors than is current

September 12, 2011

LA JOLLA, CA—Oncologists have long sought a powerful “magic bullet” that can find tumors wherever they hide in the body so that they can be imaged and then destroyed. Until recently scientists accepted the notion that such an agent, an agonist, needed to enter and accumulate in the cancerous cells to act. An international research team has now shown in cancer patients that an investigational agent that sticks onto the surface of tumor cells without triggering internalization, an antagonist, may be safer and even more effective than agonists.

One of the Salk Institute’s leading researchers, Dr. Jean Rivier, professor in The Clayton Foundation Laboratories for Peptide Biology and holder of the Frederik Paulsen Chair in Neurosciences and his Swiss collaborator, Dr. Jean Claude Reubi, University of Berne and Adjunct Professor at Salk, co-authored a pilot study, published in the September issue of the Journal of Nuclear Medicine, of five patients and demonstrated that their “antagonist”, ¹¹¹In-DOTA-BASS, outperformed the “agonist” agent, OctreoScan, that is widely used in the clinic to image neuroendocrine tumors bearing somatostatin receptors.

“This is the first proof of principle in humans that labeled peptide antagonists can effectively image tumors. Additional research suggests that we could one day use a different radioactive metal to effectively kill the tumors,” said Dr. Rivier.

Dr. Reubi, a molecular pathologist, and Dr. Rivier, a chemist, collaborated in the design and selection of ^natIn-DOTA-BASS for human testing, and Dr. Helmut R. Maecke, a radio chemist, loaded DOTA-BASS with its radioactive marker and tested the compound before use in human. Afterward, the “first in man” study with the radioactive loaded DOTA-BASS was performed at the University Hospital in Freiburgby Drs. Damian Wild, Melpomeni Fani, Martin Behe, Ingo Brink, Helmut R. Maecke, and Wolfgang A. Weber.

The genesis of this study goes back to 1973, when a team of Salk researchers, which included Drs. Brazeau, Vale, Burgus, Rivier, and Roger Guillemin, a 1977 Nobel laureate, isolated and characterized somatostatin, a peptide produced by neuroendocrine glands. The scientists found that the normal function of somatostatin is to block the release of growth hormone throughout the body, which includes inhibiting the release of thyroid-stimulating hormone (TSH) from the thyroid.

Drs. Rivier, Reubi and their colleagues from Germany showed that ¹¹¹In-DOTA-BASS bound to a greater number of somatostatin receptors on cancer cells than the agonist OctreoScan, and that it did accumulate in normal tissue (liver and kidney) to a lesser extent.

The prototype antagonist therapy has been revamped, and the version studied in the Journal of Nuclear Medicine publication, ¹¹¹In-DOTA-BASS, detected 25 of 28 metastatic neuroendocrine tumors in the patients, whereas OctreoScan detected only 17.

In-DOTA-BASS has been licensed to a pharmaceutical company for clinical trial development, according to Rivier, who adds that other researchers are exploring an antagonist approach for other G-protein coupled receptors that are abundantly expressed on cancer cells.

The study was funded in part by the Swiss National Science Foundation (JCR).

关于索尔克生物研究所：
索尔克生物研究所是世界顶尖的基础研究机构之一，其国际知名的教职人员在一个独特、协作和富有创造性的环境中，深入探究生命科学的基本问题。索尔克科学家们致力于发现和指导未来几代研究人员，通过研究神经科学、遗传学、细胞和植物生物学以及相关学科，在癌症、衰老、阿尔茨海默氏症、糖尿病和传染病的认识方面做出了开创性的贡献。.

学院取得了许多成就，获得了包括诺贝尔奖和美国国家科学院院士在内的无数荣誉。该研究所由脊髓灰质炎疫苗先驱 Jonas Salk 博士于 1960 年创立，是一家独立的非营利组织和建筑地标。.

欲了解更多信息：
Journal of Nuclear Medicine
Issue: Sept 1, 2011 vol. 52 no. 9 1412-1417

(Published online Aug. 18, 2011)

Authors: Damian Wild, Melpomeni Fani, Martin Behe, Ingo Brink, Jean E.F. Rivier, Jean Claude Reubi, Helmut R. Maecke, and Wolfgang A. Weber

First Clinical Evidence That Imaging with Somatostatin Receptor Antagonists Is Feasible