Radiopharmaceutical Chemistry

Radiopharmaceutical Science is a relatively new field with a fast-growing use in clinical and drug development set-ups. For example, the application of radiopharmaceuticals in diagnosis is growing at over 10% per year worldwide (World Nuclear Association, January, 2014). In Denmark a number of major hospitals have had cyclotron facilities for years, and several are to be established within the next years. Therefore in Denmark there is an increasing demand of specialists educated and trained in developing, evaluating and using radiopharmaceuticals.

Furthermore, increased availability and novel radiopharmaceutical concepts such as e.g. endoradiotherapy, theranostics, neutron-capture therapy, or in vivo click approaches will most likely increase the use of radiopharmaceuticals in relation to diagnosis and therapy significantly. And in terms of drug development, in vivo radiopharmaceutical approaches bear the advantage to decrease the drug approval time or to select the best drug candidate for clinical trials. Thus, the use of radiopharmaceutical techniques is likely to lower drug development costs by accelerating bench to bedside timeframes by reducing the risk of failures. Due to the short half-life of the isotopes used, many radiopharmaceuticals have to be produced close to the final clinical use and the production can therefore not be outsourced.

The radiopharmaceutical chemistry profile within the MSc in Medicinal Chemistry covers the basic concepts of radiopharmaceutical sciences: From radiochemistry (labeling techniques) to biological evaluation processes, from clinical diagnostic to therapeutic applications. The profile also focuses on the impact of radioactive probes in drug design and development processes.

[18F]Altanserin is a good example to explain these activities in more detail. Altanserin is a 5-HT2A receptor antagonist that was successfully developed after intensive structure-activity relationship and in vitro/vivo evaluation studies. Applying [18F]altanserin in positron emission tomography (PET), it is possible to specifically image and quantify the 5-HT2A serotonergic receptor status in the living brain. Since this receptor is involved in many brain diseases like depression or schizophrenia, [18F]altanserin can be used to study the receptor system under different physiological conditions. This, in turn, opens up the possibility to probe receptor occupancies after a pharmacological challenge (for example with a newly developed drug) or to quantify differences in receptor binding between patient and control groups. The gained outcomes are of crucial importance in any drug development process and allow faster drug candidate selection and assessment.

PET image of [18F]altanserin. The radiopharmaceutical accumulates in 5-HT2A receptor rich regions within the human brain.

PET image of [18F]altanserin. The radiopharmaceutical accumulates in 5-HT2A receptor rich regions within the human brain.