AT Groningen, Netherlands
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Altai M.,Uppsala University | Perols A.,KTH Royal Institute of Technology | Tsourma M.,Uppsala University | Mitran B.,Uppsala University | And 8 more authors.
Journal of Nuclear Medicine | Year: 2016

Affibody molecules constitute a new class of probes for radionuclide tumor targeting. The small size of Affibody molecules is favorable for rapid localization in tumors and clearance from circulation. However, high renal reabsorption of Affibody molecules prevents the use of residualizing radiometals, including several promising low-energy β- and α-emitters, for radionuclide therapy. We tested a hypothesis that Affibody-based pretargeting mediated by a bioorthogonal interaction between trans-cyclooctene (TCO) and tetrazine would provide higher accumulation of radiometals in tumor xenografts than in the kidneys. Methods: TCO was conjugated to the anti-human epidermal growth factor receptor 2 (HER2) Affibody molecule Z2395. DOTA-tetrazine was labeled with 111In and 177Lu. In vitro pretargeting was studied in HER2- expressing SKOV-3 and BT474 cell lines. In vivo studies were performed on BALB/C nu/nu mice bearing SKOV-3 xenografts. Results: 125I-Z2395-TCO bound specifically to HER2-expressing cells in vitro with an affinity of 45 ± 16 pM. 111In-tetrazine bound specifically and selectively to Z2395-TCO pretreated cells. In vivo studies demonstrated HER2- specific 125I-Z2395-TCO accumulation in xenografts. TCO-mediated 111In-tetrazine localization was shown in tumors, when the radiolabeled tracer was injected 4 h after an injection of Z2395-TCO. At 1 h after injection, the tumor uptake of 111In-tetrazine and177Lu-tetrazine was approximately 2-fold higher than the renal uptake. Pretargeting provided more than a 56-fold reduction of renal uptake of 111In in comparison with direct targeting. Conclusion: The feasibility of Affibody-based bioorthogonal chemistry-mediated pretargeting was demonstrated. The use of pretargeting provides a substantial reduction of radiometal accumulation in kidneys, creating preconditions for palliative radionuclide therapy. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.


News Article | November 29, 2016
Site: globenewswire.com

Proprietary method in collaboration with Syncom B.V. will achieve a THC purity level of Greater than 95% NEW YORK, Nov. 29, 2016 (GLOBE NEWSWIRE) -- AXIM® Biotechnologies, Inc. (AXIM® Biotech) (OTC:AXIM), a world leader in cannabinoid research and development, today announced that it filed an IP application with the World Intellectual Property Organization (WIPO) on a proprietary method to extract THC-A (tetrahydrocannabinol acid) from cannabis plants and to achieve THC (tetrahydrocannabinol) with higher purity than conventional methods. This invention relates to a method to extract THC-A from cannabis flower using a non-polar solvent, wherein the yield is approximately 50 - 70% with regards to THC-A content in the starting material. A neutral metal salt or inorganic base solution saturated with the metal neutral salt and adjusted to basic pH enables separation of the THC-A layer and significantly increases the yield. THC-A is decarboxylated in a water/ethanol solution to give THC at a purity higher than 95%. The IP was generated in collaboration with Syncom B.V., a Netherlands-based leading company in custom synthesis solutions for pharmaceutical and biotech industry. “We are pleased to announce the IP application of our own THC extraction method. There are many THC-based products on the market but none are pure grade. Our application, developed in conjunction with Syncom, is a game changer as the extraction method produces THC in the purest form. In addition, this new method will allow us to have the highest THC yields with no heavy metals, solvents or other unwanted residues,” said George E. Anastassov, MD, DDS, MBA and Chief Executive Officer of AXIM® Biotech. “This new extraction application attests to the high competence of the AXIM research and development team, and will go a long way in supporting our mission in finding cannabinoid-derived solutions for health conditions with no known cure.” CEO of Syncom, Dr. Ton Vries adds: “Syncom is glad to have made a relevant contribution to the novel extraction of THC, we will continue in collaborating with Axim and proceed with the development of state of the art active pharmaceutical Ingredients derived from the Cannabis plant” About AXIM AXIM® Biotechnologies, Inc. (OTC:AXIM) focuses on the research, development and production of cannabis-based pharmaceutical, nutraceutical and cosmetic products. Our flagship products include CanChew, a CBD-based controlled release chewing gum, and MedChew Rx, a combination CBD/THC gum that is undergoing clinical trials for the treatment of pain and spasticity associated with multiple sclerosis. We prioritize the well-being of our customers while embracing a solid fiscal strategy. Medical Marijuana, Inc. is a major investor in AXIM. For more information, visit www.AXIMBiotech.com. About SYNCOM B.V. Syncom is a global leader in providing the pharmaceutical and biotech industries with custom synthesis solutions. Syncom has an excellent track record dating back to the foundation of the company in 1988. We count both leading global pharmaceutical companies as well as small virtual start up companies among our clients. In addition to our pharma activities we serve the diagnostic, fine chemical, electronic and pigment industries as well. For more information, visit www.syncom.nl FORWARD-LOOKING DISCLAIMER This press release may contain certain forward-looking statements and information, as defined within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, and is subject to the Safe Harbor created by those sections. This material contains statements about expected future events and/or financial results that are forward-looking in nature and subject to risks and uncertainties. Such forward-looking statements by definition involve risks, uncertainties and other factors, which may cause the actual results, performance or achievements of Axim Biotechnologies, Inc. to be materially different from the statements made herein. LEGAL DISCLOSURE AXIM® Biotechnologies does not sell or distribute any products that are in violation of the United States Controlled Substances Act (US.CSA).


Versteegen R.M.,SyMO Chemical | Rossin R.,HIGH-TECH | Ten Hoeve W.,Syncom | Janssen H.M.,SyMO Chemical | Robillard M.S.,HIGH-TECH
Angewandte Chemie - International Edition | Year: 2013

Eliminated without a trace: The fastest click reaction, the highly selective inverse-electron-demand Diels-Alder reaction, has been modified to enable selective bioorthogonal release. Thus, the click reaction of a tetrazine with a drug-bound trans-cyclooctene caused the instantaneous release of the drug and CO2 (see scheme). One possible application is the chemically triggered release, and thereby activation, of a drug from a tumor-bound antibody-drug conjugate. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Rossin R.,HIGH-TECH | Van Duijnhoven S.M.J.,HIGH-TECH | Ten Hoeve W.,Syncom | Janssen H.M.,SyMO Chemical | And 4 more authors.
Bioconjugate Chemistry | Year: 2016

The use of a bioorthogonal reaction for the selective cleavage of tumor-bound antibody-drug conjugates (ADCs) would represent a powerful new tool for ADC therapy, as it would not rely on the currently used intracellular biological activation mechanisms, thereby expanding the scope to noninternalizing cancer targets. Here we report that the recently developed inverse-electron-demand Diels-Alder pyridazine elimination reaction can provoke rapid and self-immolative release of doxorubicin from an ADC in vitro and in tumor-bearing mice. © 2016 American Chemical Society.


PubMed | HIGH-TECH, SyMO Chemical and Syncom
Type: Journal Article | Journal: Bioconjugate chemistry | Year: 2016

The use of a bioorthogonal reaction for the selective cleavage of tumor-bound antibody-drug conjugates (ADCs) would represent a powerful new tool for ADC therapy, as it would not rely on the currently used intracellular biological activation mechanisms, thereby expanding the scope to noninternalizing cancer targets. Here we report that the recently developed inverse-electron-demand Diels-Alder pyridazine elimination reaction can provoke rapid and self-immolative release of doxorubicin from an ADC in vitro and in tumor-bearing mice.

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