Project: A SPECT/CT Platform for Molecular and Structural In-Vivo Imaging in Small Animals.

A SPECT/CT Platform for Molecular and Structural In-Vivo Imaging in Small Animals.

Dit is de samenvatting van de aanvraag.

With animal Single Photon Emission Computed Tomography (SPECT) the three-dimensional localisation of radioactive tracers can be determined at extremely low concentrations (nanomolar-picomolar). By using tracers that bind to specific bio-molecules, gene and protein function in the living body can be visualized. SPECT can answer questions such as: Where did the molecules go? and: How well are the therapeutics administered to a tumor? Although some answers could also be ascertained ex-vivo, those methods require sacrificing the animal. In vivo imaging, such as SPECT, has therefore obvious advantages. Because it can follow the same animal through time, data is more statistically powerful and fewer animals are needed.X-ray Computed Tomography (CT) on the other hand is a technique that can visualise anatomy at very high spatial resolution by means of the X-ray density distribution. SPECT and CT are thus complementary techniques in the sense that one can visualise functional tracers at a very sensitive level and the other can delineate these activities with respect to the anatomy. Recently both modalities have been re-scaled to small animal imaging modalities. The current proposal is a the request for a combined small animal-SPECT/CT modality for in-vivo functional and structural imaging. With the requested unique multi-pinhole micro-SPECT/CT platform it will be possible to image non-invasively the location, duration, and magnitude of gene and protein expression in-vivo in (transgene) mouse models. In addition, it can be coupled to structural changes in follow-up studies in one animal. This in-vivo whole-body imaging platform will allow functional high-throughput screening at the cellular and molecular level. The scanner can be used for either SPECT or CT scans only, or in the combined mode for structure-function overlay, depending on application. This micro molecular imaging set up is currently introduced at several research institutes and is in general believed to revolutionize functional genomics. The requested equipment is unique in the sense that it will be the first micro SPECT/CT combination at sub millimeter resolution. In addition the three dimensional images allow digital quantification of protein or gene expression, or of morphological identification that further speed up and deepen the functional analyses of animal models. Either department of applicants collaborate with SPECT or micro-CT with many groups in and outside the Erasmus MC to study cancer related issues (Nuclear Medicine) or skeletal related issues (Orthopaedics) and operate at the international frontline of applying such equipment in their research areas. Both have developed a variety of research tools (e.g. software, tracers, animal models) to fully take advantage of this novel equipment that will be pioneered within the next decade and revolutionize the field. A multidisciplinary network of research groups at Erasmus MC, TU Delft and UMCs Utrecht and Nijmegen will directly incorporate the new equipment in their existing research lines in the fields of cancer research (tumor growth, imaging, (gene) therapy, angiogenesis, DNA repair), skeletal research (osteoporosis, osteoarthritis), cardiovascular research (gene therapy, arthrosclerotic plaques), endocrinology (neuro-endocrine tumors), and general surgery (organ transplantation). In addition, within the Erasmus MC many groups that have developed (transgenic) mouse models will start to utilise the systems for enhanced phenotyping of their models. The proposed system will therefore be an important part of the infrastructure for research of many complex diseases and traits. Given the importance of a combined micro SPECT/CT platform to further establish the existing international position of the collaborative research groups, the departments of applicants are willing to co-invest significantly in the requested equipment. We anticipate a huge spin off of the micro SPECT/CT platform both in and outside the Erasmus MC, since this imaging modality will become a crucial tool in the development of novel and next generation (radio)pharmaceuticals for imaging and therapy in the study of diseases.

So, the present proposal is a joined initiative of several departments in Erasmus MC and other Dutch groups, requesting NWO support for the acquisition of a novel SPECT/CT in-vivo imaging platform for elucidating gene function, protein expression and structural alterations in small animals.