12 de septiembre de 2011
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
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
LA JOLLA, CA—Los oncólogos han buscado durante mucho tiempo una “bala mágica” poderosa que pueda encontrar tumores dondequiera que se escondan en el cuerpo para poder ser visualizados y luego destruidos. Hasta hace poco, los científicos aceptaban la idea de que tal agente, un agonista, necesitaba entrar y acumularse en las células cancerosas para actuar. Un equipo internacional de investigación ha demostrado ahora en pacientes con cáncer que un agente experimental que se adhiere a la superficie de las células tumorales sin desencadenar la internalización, un antagonista, puede ser más seguro e incluso más efectivo que los agonistas.
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).
Acerca del Instituto Salk de Estudios Biológicos:
El Instituto Salk de Estudios Biológicos es una de las instituciones de investigación básica más destacadas del mundo, donde un cuerpo docente de prestigio internacional investiga cuestiones fundamentales de las ciencias de la vida en un entorno único, colaborativo y creativo. Centrados tanto en el descubrimiento como en la formación de las futuras generaciones de investigadores, los científicos del Salk realizan contribuciones revolucionarias a nuestra comprensión del cáncer, el envejecimiento, el Alzheimer, la diabetes y las enfermedades infecciosas mediante el estudio de la neurociencia, la genética, la biología celular y vegetal, y otras disciplinas relacionadas.
Los logros del cuerpo docente han sido reconocidos con numerosos galardones, entre los que se incluyen premios Nobel y la pertenencia a la Academia Nacional de Ciencias. Fundado en 1960 por el Dr. Jonas Salk, pionero en la vacuna contra la poliomielitis, el Instituto es una organización independiente sin fines de lucro y un hito arquitectónico.
For more information:
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
Oficina de Comunicaciones
Tel.: (858) 453-4100
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