Keynotes
The future of Molecular Imaging-
Images or information using tracers to explore biology?
Sunday, August 28, 2011
Bengt Långström
Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala; Imperial
College, London and Syddansk University, Odense, Denmark
Molecular Imaging has been interpreted from a semantic perspective in many ways and that is in itself an interesting question to address.
If we focus on the use of the labelled compounds, which is covered within PET as a tracer technology, Molecular Imaging is an on-going interesting and maybe scaring development.
In the lecture there will be a discussion on the use of labelled compounds, perspectives on molecular design and impact on the applications. Is the focus to label compounds, using the unique properties of PET tracers with regard to the fact that we can produce
many of these compounds in high specific activity, to obtain results reflecting the fate of these labelled molecules? Or maybe the focus should be on using the labelled compounds in order to understand the biology?
I will argue that the field where radiochemistry and a meeting like ISRS should play an important and a future role is not only to label compounds but also to develop methods and technology in order to explore and validate the biological information we may
obtain. We should remember that the most unique characteristics of PET are to be found in the fact that we have access to radionuclides like 15O, 13N and most of all 11C. We have a unique possibility to develop and explore tracer tools in order to understand
the biology. To recall that especially these are radionuclides of key elements of life giving us tools to be used as well in in vivo biology dynamics studies.
Of course the access to other compounds with a radiolabel of 18F, and interesting radiometals like 68Ga including many Cu radioisotopes attached to macromolecules is of significant value as tools to explore the biology.
It is time to regain a wider perspective of Molecular Imaging discussing/ validating more the content and biological information of images, so more focus on quantification then resolution however without neglecting the latter.
Molecular Imaging From an Industry Perspective
Monday, August 29, 2011
Matthias Friebe
Bayer HealthCare, Global Drug Discovery, Berlin, Germany
To further improve therapeutic outcome for our patients we have to continue to strive for a better and more specific diagnosis. This is not only true for an earlier detection of diseases but also for a better staging and restaging. Characterization of the receptor- or metabolic pathways leads to a better stratification, early response assessment and therapy monitoring. Especially hybrid imaging technologies like PET/CT and MRI/PET allowing for high detection sensitivity at a high spatial resolution will play an increasing role in diagnostic imaging.
Innovative molecular imaging probes are currently in development addressing major unmet diagnostic needs in oncology (i.e. prostate cancer staging, therapy response monitoring in lung cancer, and the detection of brain metastases), neurodegenerative diseases (i.e. early imaging of Alzheimer disease), and cardiovascular diseases (i.e. Thrombus imaging).
On the basis of new proprietary compounds deriving from our research pipeline the opportunities of molecular imaging from an industry perspective will be discussed.
What are the clinical needs for nuclear imaging from the perspective of a neurologist?
Tuesday, August 30, 2011
Andreas H. Jacobs
European Institute for Molecular Imaging and Department of Nuclear Medicine at the
University Hospital of the Westphalian Wilhelms-University Münster, Münster, Germany
Nuclear imaging aims at the non-invasive detection, quantification and longitudinal follow-up determination of disease specific molecular alterations with highest sensitivity in controls and patients. Based on various pathophysiological processes causing diseases of the central nervous system (CNS) various molecular targets for imaging are of importance: (i) cerebral ischemia, acute and subacute changes cause early and delayed neuronal death; (ii) neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease (AD, PD), pathological protein depositions cause a slowly progressive neuronal degeneration and loss of specific neuronal populations; and (iii) brain tumors, uncontrolled cell proliferation cause progressive destruction of functionally important neuronal tissue. In all of these diseases, the interplay between the neuronal, glial, vascular, and immune components of the neurovascular unit is being recognized to play a major role in disease pathogenesis.
Challenges for nuclear imaging of diseases of the CNS comprise (i) the development of compounds passing the intact blood brain barrier; (ii) access to multiple radiotracers targeting more than one molecular target of the disease; (iii) access to repeat productions to enable the non-invasive assessment of disease dynamics and effects of therapy; (iv) strong interdisciplinary interplay between basic (radio)chemists, computer scientists and clinicians to enable translation of new compound developments into clinical value. New developments include also multi-modality probes which allow direct comparisons with and joint applications of other imaging modalities, such as optical imaging and MRI (e.g. PET-MR).
Radiopharmaceutical Chemistry and Medicinal Chemistry: Where Do They Meet and How Can Mutual Benefit be Obtained
Wednesday, August 31, 2011
John Katzenellenbogen
University of Illinois at Urbana-Champaign, Illinois, USA
There is a dynamic interplay between medicinal chemistry, which deals with drug activities, and radiopharmaceutical chemistry, which deals with radioisotope distributions, with each providing leads (and possibly misleads) to the other in terms of structure-activity relationships, mechanism of action, and pharmacokinetic and pharmacodynamic factors. In this talk, I will explore some core themes, from my experience and that of others, to illustrate how the search for a new radiopharmaceutical agent often begins within the context of relevant medicinal chemistry and—as it progresses to success—can often reveal new aspects of drug action that are not observable from standard medicinal and pharmaceutical chemistry investigations. While the flow of information from medicinal chemistry to radiopharmaceutical chemistry is well recognized and appreciated, it is less clear that medicinal chemistry has learned as much as it can from studies of radiopharmaceutical agents. This presents both a challenge and an opportunity to investigators in our field.
GMP and radiochemistry, what we must do, what we could do without, what should be improved
Thursday, September 1, 2011
Gerrit Westera
Retired from University Hospital Zürich, Zürich, Switzerland
GMP rules have from their onset given rise to heated discussions amongst radio(pharmaceutical) chemists and continue to do so (radiopharmacists are of a more obliging attitude).
The GMP requirements we have to fulfil for every charge of product will be discussed in terms of their usefulness, defined as how they improve patient safety.
It will be shown that the focus should be shifted from quality control for every single lot of product to controlling the production processes in terms of safe procedures.
The frequency of tests, which are performed for formal reasons but which do not increase our knowledge of the quality of the product, should (if they can not be abolished altogether) be restricted to the validation phase of product development and occasional revalidations.
Analytical tests (chemical, radiochemical), the results of which are only available after the radiopharmaceutical has already been injected should be restricted to the validation phase of product development and occasional revalidation. If possible parameters should be found which provide relevant information to allow for parametric release of the product.
Sterility testing on the products is also available only long after application of the product. If possible parameters should be found which immediately provide relevant information on biological quality to allow for parametric release of the product rather than formal release weeks after application.
Useful in terms of product safety is repeated training of personnel and frequent control by media fill of the production equipment (if possible), procedures and personnel.