Fluorination of anticancer peptide drug conjugates
- Reference number
- ID21-0069
- Project leader
- Szabo, Kalman
- Start and end dates
- 220101-261231
- Amount granted
- 2 500 000 SEK
- Administrative organization
- Stockholm University
- Research area
- Life Sciences
Summary
This project aims study and development of new nitrogen based alkylating anticancer drugs, which are used for example treatment of lymphatic cancers. Currently one of the main hinder of the efficient development of these anticancer drugs is luck of mechanistic insights in the uptake and organ/tissue distribution of these drugs. The main objective of this project is application of Positron Emission Tomography (PET) for these mechanistic studies using fluorine-18 tracers. This requires development of new late-stage fluorination methodologies for synthesis of the anticancer agents. Subsequently, this methodology is translated to fluorine-18 isotope labeling technique. Finally, PET imaging studies will be used to study the in vivo distribution of the fluorine-18 labelled anticancer drugs in leaving organisms. The expected results involve development of a new class of fluorine-18 PET tracers. Using of PET imaging results a new generation of anticancer drugs can be developed for efficient and selective treatment of lymphoma and other forms of cancer. The Ph.D. studies will be done at Stockholm University and Oncopeptides under supervision of researchers (Prof. Kálmán J. Szabó and Dr. Fredrik Lehmann) with completing expertise in organofluorine chemistry and drug development. The strong and successful academic and industrial environments guaranties the success of the industrial Ph.D. education project.
Popular science description
Cardiovascular diseases and cancer are the most common causes for mortality. Medical treatment of cancer imposes large psychosocial and economic burden to the society. The American cancer society estimated that cancer has an annual worldwide economic impact of $895 billion (1.5% of gross domestic product), which larger than heart diseases. The latest publication from Cancerfonden and Socialstyrelsen reports 57 726 newly diagnosed cancer patients and approx. 22 000 cases of death in 2011. The steady improvements in therapy have already led to a significant increase of 5-year and 10-year survival rates to ca. 72% and 65%, respectively. Apparently, improved cancer therapy is very important for the society for decreasing of the patient's suffering by improving the life quality and reduction of the death cases. Milder therapies by combination of radiation therapy, surgery and specific drugs are the most desired. The specifity of the drugs can be increased by conscious drug design based on understanding of the action, distribution and uptake of the drugs in the living organisms. The proposed project is focused on study and development of anticancer drugs. Nitrogen based alkylating agents are commonly used in treatment of lymphomas. The study of the biological effects of these drug substances will be studied by Positron Emission Tomography (PET). PET is suitable for in vivo studies of biochemical processes. The PET studies require fluorine-18 labelled derivatives of the anticancer drugs. Fluorine-18 is a positron emitting nucleus with a relatively short half-life (110 minutes). The short life-life imposes a high challenge for synthesis and handling of fluorine-18 labelled compounds. The Ph.D. student working with the project will participate in development of new methodology for fluorine-18 labelled radiotracers and evaluation of the PET imaging studies. Subsequently, new methodology can be developed for synthesis of the next generation anticancer drugs. The Ph.D. student will be supervised by Prof. Kálmán J. Szabó (Stockholm University) and Dr. Fredrik Lehmann (Oncopeptides), having completing expertise in organic fluorine chemistry and drug design. Notably Oncopeptide's anticancer drug Melflufene was recently approved by the U.S. Food and Drug Administration.