Imaging


I


n vivo imaging is increasingly deployed across the drug development process, with applica- bility in target identification, compound opti- misation and pre-Phase I studies. In vivo imaging has been described as bridging the gap between in vitro exploratory and in vivo clinical research, facilitating the direct and fast transfer of preclini- cal studies on animal models to clinical investiga- tion in man. There are numerous instances across therapeutic areas where preclinical imaging has proved valuable in drug development, for exam- ple: in target localisation, quantification of dis- ease, disease phenotyping, mode of action studies, efficacy studies; in vivo pharmacokinetics and dosing and treatment models to name but a few. Non-invasive imaging is a rapidly advancing field, with innovation in dedicated small animal imag- ing technologies now paralleling their clinical equivalents. Multiple imaging modalities are now available for small animal studies which when combined complement each other to provide information on molecular features, metabolism and function all within the context of anatomical structure and localisation. New imaging systems and developments in animal models, reagent chemistries and biomarkers suitable for cell labelling continue to ensure the rapid growth in the field. With this in mind HTStec initiated in January 2011 a market study on in vivo preclini- cal imaging, as part of its ongoing tracking of emerging life science marketplaces1. This survey and the associated vendor contributions serve as the basis for this review.


Key diseases/therapeutic areas targeted The key diseases/therapeutic areas targeted with in vivo preclinical imaging by survey respondents were oncology/cancer (70% targeting). This was followed by inflammatory disease/autoimmune (36% targeting); neurology/CNS/neurodegenera- tion/pain (32% targeting) and then cardiovascular (25% targeting) (Figure 1).


Main applications of in vivo preclinical imaging


Monitoring treatment response for early indica- tions of efficacy was rated as the main application of in vivo preclinical imaging (68% investigating). This was followed by biodistribution, determining drug/target engagement (59% investigating); can- cer cell detection (49% investigating); biomarkers (41% investigating); and then longitudinal studies (39% investigating). Least investigated was epige- netics, monitoring drugs that affect chromatin (4% investigating) (Figure 2).


Drug Discovery World Summer 2011


Figure 1: Key diseases/therapeutic areas targeted with preclinical imaging


Neurology/CNS/Neurodegeneration/Pain Inflammatory Disease/Autoimmune Oncology/Cancer


Metabolic Disease/Diabetes Cardiovascular Disease


Immunology & Transplantation Biology Drug Metabolism Studies Stem cell Biology


Bone and Skeletal Disease Respiratory/Pulmonary Disease Infectious Diseases Toxicology


Gene Therapy 25% 21% 20%


18% 18%


17% 17% 17%


14% 12%


0% 10% 20% 30% 40% 50% 60% 70% 80% % Responding


© HTStec 2011 70% 36% 32%


Figure 2: Main applications investigated with in vivo preclinical imaging


Biodistribution, determining drug/target engagement Monitoring treatment response, early indications of efficacy


Cancer cell detection


Dose optimisation, scheduling and optimal dosing regimen Define mechanism of action Receptor targeting Longitudinal studies Biomarkers


Vascular/lymphatic imaging Tracking transplanted cells


Transporter targeting Structural imaging


Epigenetics – monitoring drugs that affect chromatin Tissue regeneration Stem cells


16% 16%


4%


0% 10% 20% 30% 40% 50% 60% 70% % Responding


© HTStec 2011 24% 21% 28% 41% 39%


36% 36%


32% 29% 49% 68% 59%


Figure 3: Most used single imaging modality today


Positron emission tomography (PET) Magnetic resonance imaging (MRI) Optical (bioluminescence/luminescence)


Single photon emission computed tomography (SPECT) Optical (fluorescence)


X-ray computed tomography (CT) Ultrasound (US)


X-ray 0% © HTStec 2011 28% 23% 20% 19%


3% 3% 3%


1%


5% 10% 15% 20% 25% 30% % Responding


59


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92