20PharmaGenomicsMay 2004Industry Watch Medical Imaging in DrugDiscovery — Part IIMolecular imaging is beginning to be applied to pre-clinical drug development efforts,and a number of new companies are poised to serve this market, touting theirmolecular imaging technologies as specifically aiding drug development.Stan N. Finkelstein, Anthony J. Sinskey and Scott M. CooperIn our last column (PharmaGenomics 4[1], 16–19 [2004]),we began to explore the shift to a broader-than-diagnosticview of the value of imaging technologies. It stands to rea-son that imaging should play some broader role. After all, asRobert Dunkle reports in a recent article, “Up to 70% of theexperiments in pharmaceutical research and development re-sult in an image as an output” (1).Of course, Dunkle is referring to virtually every kind ofimage one could imagine, from a snapshot taken of a slidethrough a microscope to the kinds of magnetic resonance im-ages (MRIs), computed tomography (CT) scans, positronemission tomography (PET) scans, X-rays and ultrasoundswe discussed last month. But even considering only “high-tech” imaging, its use in discovery and development definitelyis on the rise.In this column, we want to explore issues related to imagingat the molecular level. Molecular imaging merges the moderntools of molecular and cell biology with state-of-the-art tech-nology. The goal is to develop technologies and assays forimaging molecular and cellular events in living organisms,thus aiding in finding better methods for studying biologicalprocesses. It’s truly interdisciplinary: “The term ‘molecularimaging’ implies the convergence of multiple image-capturetechniques, basic cell/molecular biology, chemistry, medicine,pharmacology, medical physics, biomathematics and bioinfor-matics into a new imaging paradigm” (2).We’re interested in what molecular imaging can do for drugdevelopment and discovery. Can it improve the drug develop-ment process? In what specific activities could it be most use-ful? One note: we’re indebted to David Wine, a graduate stu-dent at the MIT Sloan School of Management, who producedan outstanding overview of the issues in a literature review heprepared for a class — Research Themes in Management ofTe c hnology (3).A New DisciplineThe first thing to say about molecular imaging is that it is rela-tively new. As a scientific discipline, it dates back roughly to 1993,although it is growing in scope and influence. Medline andPubMed only recently added “molecular imaging” as a subjectterm.Three dedicated journals have emerged in the past threeyears, and there are three specialized annual scientific congressesnow devoted to the discipline. The Society for Molecular Imaging(SMI, Stanford, California, USA) was founded in 2000 as an “in-ternational scientific educational organization whose purpose isto advance our understanding of biology and medicine throughnoninvasive in vivo investigation of cellular molecular events in-volved in normal and pathologic processes” (4).Accelerating pre-clinical drug development is one of thekey areas of focus for scientists involved in molecular imaging.It is one of three “overarching areas” in which molecularimaging has advanced dramatically of late, and was one of themain topics at the SMI’s annual meeting in San Francisco,California, in August 2003. As the society’s press release forthe meeting explains:“Problems in pre-clinical drug development have been ad-dressed through advances in [molecular imaging]. First, typi-cal assays for drug efficacy have required the excision of tissue,biopsy or necropsy, and these assays are slow and subject tosampling errors. Relatively inexpensive tools have been in-vented to produce rapid whole-body analyses, which providebetter information more rapidly,thus enabling more sophisti-cated drug studies in animals. These advanced approaches,currently used in animal studies, will improve the design ofclinical studies and ultimately make better drugs availableStan N. Finkelsteinand Anthony J. Sinskeyare co-directors of The Program on the Pharmaceutical Industry (POPI) inCambridge, Massachusetts, USA. Finkelstein also is a senior researchscientist at MIT Sloan School of Management in Cambridge. Sinskey isprofessor of microbiology at MIT in Cambridge. Scott M. Cooper,an affiliate and frequent collaborator of POPI researchers, is a visitingscholar in the MIT Department of Biology.sooner. Second, understanding themechanisms of action for drugs at themolecular level is key to effective develop-ment of novel therapeutic strategies.[Molecular imaging] enables analysis ofthe target as well as the delivery of thetherapy” (5).Molecular imaging involves severaltechnologies, including single photonemission computed tomography(SPECT), PET, MRI, CT and ultra-sound. According to the Society of Non-invasive Imaging in Drug Development(SNIDD), which is an institute of theAcademy of Molecular Imaging (LosAngeles, California, USA), these “non-invasive imaging techniques can be usedto obtain information on in vivo bio-chemistry and physiology in experimen-tal animals and man that cannot be ob-tained in any other way. As applied todrug discovery and development, infor-mation obtainable via imaging can bedivided into four categories: 1) determi-nation of desirable, pharmacological ef-fects or undesirable side effects (i.e., theeffect of the drug candidate on in vivobiochemistry and physiology); 2) the in-teraction of a drug or drug candidatewith the desired target (e.g., receptor,enzyme or transport system), includingdose occupancy relationships and ki-netic information; 3) the delivery of adrug to a specific target and 4) the ab-sorption, distribution, metabolism andelimination of the labeled drug candi-date” (6).What About Drug Development?One of the keys to molecular imaging’svalue in drug development is probes,which provide the imaging signal orimage contrast in most molecular imag-ing assays. They are similar to stainsused in histological analysis of tissuesamples, but unlike stains, they are in-jected into living subjects to create im-ages of specific biological or molecularevents. Many probes are discovered bychance, but “recent advances in the drugdiscovery process will aid in future se-lection and/or rational design of newerprobes through combinatorial chem-istry and high-throughput testing. It isanticipated that increasing multidisci-plinary interactions between imagingresearch groups and