Urs Hafeli
About the Principal Investigator
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Training
| Degree: | B.S., Pharmacy |
| Institution: | Federal Institute of Technology, Zurich |
| Year: | 1986 |
| Degree: | Ph.D., Pharmacy |
| Institution: | Paul Scherrer Institute / Federal Institute of Technology, Zurich |
| Year: | 1989 |
Current Position
| Position: | Associate Professor |
Links
Research Interests
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About the Lab
The research in my lab is primarily directed at fighting cancer with radioactive pharmaceuticals and the development of diagnostic radiopharmaceuticals to be used in different Nuclear Medicine procedures. We also enjoy exploiting nanotechnology and microtechnology for different drug delivery applications, including the development of painless microneedles and the use of microfluidics for the preparation of monosized microspheres. Under the guidance of Dr. Kathy Saatchi, our lab has a strong chemistry base that encompasses organic, coordination and polymer chemistry. Our research includes the entire spectrum of drug research from the synthesis and (radio- and other) labelling of new molecules; the preparation of drug delivery carriers such as microspheres, antibodies, and polymers; their careful evaluation both in vitro and in vivo, and finally their efficacy testing in different in vivo models accompanied by imaging with many different imaging modalities (SPECT, PET, CT, MRI, optical imaging).
Projects
Radiopharmaceuticals, the general name for radiolabelled diagnostic and therapeutic agents, can take many different shapes including particles sized from tens of nanometers (= nanospheres) up to about 100 micrometers (= microspheres), viscous solutions and micellar/liposomal suspensions, sheets, metal implants such as stents (metal or plastic coils), and biodegradable films. Our lab is interested in preparing radioactively labelled drug delivery vehicles and using them to kill tumours and prevent their reoccurrence.
The main radioactive isotopes we are currently working with are the beta-emitters rhenium-188 (Re-188) and yttrium-90 (Y-90), and their diagnostic counterparts technetium-99m (Tc-99m) and indium-111 (In-111). For imaging purposes we use also the PET isotopes fluorine-18 (F-18) and gallium-68 (Ga-68). Connecting the radioisotopes to a molecule or polymer, microsphere or antibody is not always easy, and we use isotope-specific chelators for this purpose. Many of the chelators are bound to biodegradable polymers - “polymers with a grip” - and tested in vivo, in the form of microspheres and films.
In another project, we prepare radiolabelled anti-mesothelin antibodies for targeted therapy of mesothelioma (cancer from asbestos exposure) as well as pancreas cancer, which are both very difficult to treat. Both tumours express mesothelin receptors which we use as targets for antimesothelin antibodies either for imaging purposes or then with antibody-bound Re-188 radioactivity to irradiate and destroy the cancerous cells.
Magnetic Microspheres
The main problem of cancer therapy is not the lack of efficient drugs, but that these drugs are very difficult to concentrate in the tumour tissue without leading to toxic effects on neighbouring organs and tissues.
One method to concentrate drugs is by magnetic drug delivery with particulate carriers, an efficient method of delivering a drug to a localized disease site. In magnetic targeting, a drug or therapeutic radioisotope is bound to a magnetic compound, injected into a patient’s blood stream, and then stopped with a powerful magnetic field in the target area. Depending on the type of drug, it is then slowly released from the magnetic carriers (e.g., release of chemotherapeutic drugs from magnetic microspheres) or confers a local effect (e.g., irradiation from radioactive microspheres; hyperthermia with magnetic nanoparticles). Small amounts of drug targeted magnetically to localized disease sites can thus possibly replace large amounts of freely circulating and toxic drug and reach effective and up to several-fold increased localized drug levels.
Monosized Microspheres
In our lab, we are also investigating new ways of preparing uniform magnetic and non-magnetic microspheres with a diameter of 1.0 µm, made from biodegradable materials and appropriate for intravascular human use. Many different technologies are used to prepare monosized microspheres. Classic solvent evaporation methods produce size distributions with CV’s (coefficient of variation) of >30%, while our flow focusing method produces monosized microspheres (CV's <3%).
Furthermore, we are interested in evaluating the toxicity of both the final microspheres and the incorporated magnetic nanoparticles which give them their magnetic properties. These investigations are based on cell viability experiments and confocal microscopy investigations over time in cell cultures.
Selected Publications
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