Urs Otto Häfeli
13, Bygning: 13-4-406
2100 København Ø
Drug Delivery and Biophysics of Biopharmaceuticals
13, Bygning: 13-3-318
2100 København Ø
Primary Fields of Research: An Overview
The Hafeli lab is interested in providing tools to develop diagnostic pharmaceuticals to detect cancer and to then fight this disease with radioactive pharmaceuticals, in combination with more standard anticancer agents. Imaging methods used include MRI, SPECT, PET, CT, ultrasound, and optical imaging. Dr. Hafeli is also investigating the use of magnetic drug targeting to deliver pharmaceuticals in a defined and concentrated way and has been chairing an international conference in this field since 1996. Other active fields of research are the development of vaccines that do not require booster shots, and the development and use of microneedles for painfree and dose-sparing vaccinations, improved pharmacokinetics for certain biologics, melanoma and other local skin treatments. Microneedles are also useful for therapeutic drug monitoring in interstitial fluid.
Radiopharmaceuticals and SPECT/PET/CT Imaging
Radioactive drugs can be used for many therapeutic purposes such as cancer treatment or scar prevention. Radiopharmaceuticals, the general name for radiolabeled 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, and even metal implants such as stents (metal or plastic coils) or foils. The Hafeli lab is interested in preparing radioactively labelled drug delivery vehicles and using them to kill tumours and prevent their reoccurrence. The image to the right shows a radiopharmaceutical that we recently prepared and tested as a lung perfusion imaging agent. In a healthy animal, it perfectly outlines the lungs, without uptake in any other organ.
The main radioactive isotopes we are currently investigating are the beta-emitters rhenium-188 (Re-188), yttrium-90 (Y-90), and their diagnostic counterparts technetium-99m (Tc-99m), indium-111 (In-111) and gallium-67 (Ga-67). Some PET isotope are also included, such as fluorine-18 (F-18), gallium-68 (Ga-68), and zirconium-89 (Zr-89). We also use other isotopes such as iodine-125 (I-125), iodine-123 (I-123), palladium-103 (Pd-103) and iridium-192 (Ir-192).
Radioactive imaging is done on a VECTor SPECT/PET/CT scanner from MILABS instrument which allows for simultaneous PET and SPECT imaging at very high resolutions (less than 0.5 mm). The scanner is used to develop novel radiopharmaceuticals, to investigate diseases, to carry out brain research, and to enhance imaging physics and processing.
Magnetic Nanoparticles and 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 accomplish this is by magnetic drug delivery with particulate carriers, a very efficient method of delivering a drug to a localized disease site. The figure to the right highlights the concept of magnetic targeting by comparing it with systemic drug delivery. 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 drug and reach effective and up to several-fold increased localized drug levels.
The Hafeli lab is currently investigating new ways of preparing uniform magnetic microspheres with a microchip based flow focusing method. In this method, the polymer is dissolved and pumped through an orifice where the liquid stream breaks up into monosized droplets. The solvent is then extracted into the surrounding water phase, so that each droplet turns into a microsphere made from biodegradable materials and appropriate for human use. We are also interested in evaluating the toxicity of the whole microspheres and the small magnetic nanoparticles which give them their magnetic properties. These investigations are based on cell survival experiments and confocal microscopy investigations over time in cell cultures.
Drug Delivery with Microneedles
The Hafeli lab uses biocompatible metallic microneedles of typically 450 µm high for the delivery of drugs and the in situ detection of therapeutically monitored drugs. Microneedles allow for the penetration of the skin without touching the (deeper) nerve endings, and thus permit pain-free drug delivery to areas in the skin. From there, the drug can either diffuse to the blood capillaries which distributes it to other organs and tissues, or it can exert a local effect. The best example for the latter is the use of vaccines bound to nanoparticles, which stay in the epidermis after painless injection and involve the immune system to generate protection against many different bacterial and viral diseases.
The metallic hollow microneedles to the right can be easily made into large arrays. To obtain the optimal microneedle shape that easily penetrates skin, we built an artificial skin model made from different transparent layers, which together with a purpose-built test station allows us to optically observe the needle passing through the different skin layers while at the same time measuring the applied forces.
Undervisnings- og vejledningsområder
Diagnostic Imaging and Radiopharmaceuticals
A 2-week long intensive block course for graduate students. It covers radiation-related, optical, and other imaging methods (SPECT, PET, CT, MRI, microscopy, ultrasound) and their application in research. May 8-19, 2017, in Vancouver, Canada. Check out the syllabus. If interested, email, it will fill soon.
Undergraduate Pharmaceutics Course
Bachelor and Master Thesis