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).
Andy Hoang | EurekAlert!
Research offers clues for improved influenza vaccine design
09.04.2018 | NIH/National Institute of Allergy and Infectious Diseases
Injecting gene cocktail into mouse pancreas leads to humanlike tumors
06.04.2018 | University of Texas Health Science Center at San Antonio
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.
Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
19.04.2018 | Materials Sciences
19.04.2018 | Physics and Astronomy
19.04.2018 | Physics and Astronomy