Nuclear Medicine - Article Example

Journal Article Imaging of Gene Expression in Live Pancreatic Islet Cell Lines Using Dual-Isotope SPECT. Joo Ho Tai1, Binh Nguyen1, R. Glenn Wells2, Michael S. Kovacs1, Rebecca McGirr1, Frank S. Prato1, Timothy G. Morgan3 and Savita Dhanvantari1 Journal of Nuclear Medicine, 2008: Vol. 49 No. 1 94-102. Statement of the issue: The journal article presents a research study of the applications of nuclear medicine technologies to molecular biology research on gene expression. This represents a combinatorial approach to molecular medicine to produce precise, quantitative data on the gene expression profile of specific cell and tissue types. The nuclear medicine technology involves the use of dual-isotope single photon emission computed tomography (SPECT) and computerized tomography (CT) scanning to detect reporter gene expression in pancreatic islet cells. The application of this technology may provide important insights into the molecular and genetic basis of tissue function in normal and disease states. Content Summary: The research studies reported in this journal article involve an analysis of gene expression profiles in pancreatic islet cells using the tools of nuclear medicine to measure levels of gene activity in precise anatomical locations within the tissue using in vivo that permit the assessment of function within a relevant physiological context. The use of dual isotope-SPECT facilitates the simultaneous assessment of the levels of activity of multiple genes within a cell which provides a realistic assessment of gene expression profiles that define the “signature” of gene activity within a particular tissue in normal versus disease states. The present study involved an analysis of reporter gene expression by SPECT/CT in pancreatic islet cells following their transplantation to a site next to the kidney capsule. By analyzing the radioactive products of reporter gene activity, it was possible to explore the level of metabolic activity of the islet cells in vivo. They utilized multi-isotope SPECT to assess the functions of multiple genes simultaneously. Whereas PET imaging can only be used to assess the functions of one gene at a time the multi-imaging technology of SPECT facilitates a more complete examination of gene expression in the tissue. The goal of this research is to develop this methodology to assess the functions of pancreatic islet cells in patients with diabetes. Differential levels of gene expression characterize normal versus disease states. When combined with magnetic resonance imaging (MRI), positron emission tomography (PET), or bioluminescence, the technology can be applied to long-term longitudinal clinical studies of therapeutic responses in patients with diabetes. The authors hope to implement this technology to assess therapeutic responses in patients with diabetes and also to monitor the activity and functions of transplanted pancreatic islet cells with the goal of restoring insulin production. Response: The authors of this research study produced data that support the implementation of SPECT/CT assessment of gene expression levels in an in vivo setting. The rationale for this type of assessment is that it provides a highly sensitive tool to assess the levels of activity of multiple genes simultaneously by using isotopes with different emission spectra. Its promise is enhanced if the technology is combined with the use of MRI/PET scanning for longer term assessment. While the results of the research showed that SPECT/CT assessment produces quantitative data relevant to the gene expression profile and anatomical location of pancreatic islet cells, its clinical applications are somewhat uncertain. The assessment tools require a significant amount of radioactive exposure of the target tissue, even though the half-life of the radioisotopes used is short. In addition, normal cell activities and gene expression may be affected by the presence of the radioactive isotopes in the cell. The present study utilized transfected reporter gene activity as a measure of gene expression levels. These results might not be easily duplicated in the context of normal cell gene expression parameters. Implications for the field of nuclear medicine: The current status of SPECT/CT imaging technology suggests that its major application should be in basic pre-clinical research to assess the potential efficacy of experimental therapeutics and tissue transplantation studies as a prelude to their introduction to human patients. The potential effects of the radioisotope on pancreatic function and survival would preclude its current direct application to patient studies. In the future, the use of lower intensity emitting radioisotope labels may permit the use of this technology in tracking the localization and levels of gene expression in transplanted pancreatic tissue in patients with diabetes. Journal Article #2: Increased Serotonin and Dopamine Transporter Binding in Psychotropic Medication–Naïve Patients with Generalized Social Anxiety Disorder Shown by 123I-β-(4-Iodophenyl)-Tropane SPECT Nic J. van der Wee1, J. Frederieke van Veen1, Henk Stevens2, Irene M. van Vliet1, Peter P. van Rijk2 and Herman G. Westenberg1 Journal of Nuclear Medicine, 2008: Vol. 49 No. 5 757-763. Statement of the issue: This clinical research study involved an assessment of the neurotransmitter status in patients with social anxiety disorder using single photon emission computed tomography (SPECT) imaging technology. The assessment involved the binding of serotonin and dopamine transporters to a radiolabeled isotope (123-beta-(4-iodophenyl) tropane. The data were collected from a group of patients diagnosed with social anxiety disorder and compared to age-matched individuals without this disorder who served as controls. The goal of this study was to determine the potential of SPECT imaging technologies to detect differences in the serotonergic and dopaminergic systems of individuals with social anxiety disorder that might be causally linked to this psychological disorder. Content Summary: This research study involved an attempt to assess potential biochemical abnormalities in central nervous system neurotransmitter function in patients with social anxiety disorder. Most therapeutic to this order involve an empirical assessment of the effectiveness of medications that affect neurotransmitter function without concrete knowledge of the biochemical basis of this disorder. The authors carried out a small scale clinical research study utilizing SPECT assessment to explore its potential in assessing neurotransmitter function in individuals with this disorder with the hope that this information could be used to design rational therapeutic approaches to social anxiety disorder. The clinical study involved the use of 123-I-CIT SPECT analysis to assess DAT and 5-HT activity in the brain. The results of this study indicated that there was a significantly greater binding activity for 5-hydroxytryptamine (5-HTT) in the thalamus and dopamine transporter (DAT) in the striatum than in normal controls. The increased levels of binding activities were not quantitatively linked to the severity of the disorder. Higher levels of binding suggest that lower levels of the neurotransmitter are present. The data therefore indicate that these patients have reduced levels of 5-HTT. According to the authors, this was the first research study of its kind to link 5-HTT to social anxiety disorder. These data implicate the striatal thalamic compartment of the brain in the pathophysiology of this disorder. Moreover, the data provide an explanation for the efficacy of SSRIs in alleviating the symptoms of social anxiety disorder. Response: The clinical study identified significant difference in neurotransmitter physiology between individuals with social anxiety disorder and control patients with normal social function skills. This finding is significant, as it indicates that SPECT imaging may be developed further as a useful tool for the biochemical assessment of psychological disorders, an area that has been refractory to clinical assessment using conventional analytical tools. Furthermore, the finding of lower levels of 5-HT activity in the brains of individuals with social anxiety disorder is consistent with typical patient responses to SSRIs which act on this neurotransmitter system. The findings are also consistent with genetic studies that suggest that extremely shy individuals frequently possess a 5-HT promoter mutation that may affect levels of protein produced by the expression of this gene. On the other hand, additional studies of patients with social anxiety disorder by PSPECT imaging have produced different and contradictory results indicating a primary deficit in DAT signaling mechanisms in the brains of patients with social anxiety disorder. Moreover, the sensitivity of brain activity measurements using SPECT technology is not as great as that obtained using PET imaging of brain function. These observations suggest that the technology has not yet been sufficiently developed for its clinical implementation on a widespread basis at this time. Implications for the field of nuclear medicine: The use of SPECT imaging studies to assess brain metabolism may serve as an important tool for the further exploration of neurotransmitter and biochemical abnormalities that may cause psychological conditions. Such determinations of the biochemical pathophysiology associated with specific psychological disorders may lead to the development of new and better medications to treat these disorders. However, the research study findings using the SPECT technology have produced conflicting and contradictory findings in different clinical trials which question their reliability. Further preclinical and clinical research studies are needed to quantitate the use of specific probes to assess functional neurotransmitter activity in the brain before this nuclear medicine approach can be successfully implemented as a diagnostic tool for patients with social anxiety disorder. Read More