Focal Spot, Summer 1999

https://digitalcommons.wustl.edu/focal_spot_archives/1082/thumbnail.jp

Imaging and Modeling of Myocardial Metabolism

Current imaging methods have focused on evaluation of myocardial anatomy and function. However, since myocardial metabolism and function are interrelated, metabolic myocardial imaging techniques, such as positron emission tomography, single photon emission tomography, and magnetic resonance spectroscopy present novel opportunities for probing myocardial pathology and developing new therapeutic approaches. Potential clinical applications of metabolic imaging include hypertensive and ischemic heart disease, heart failure, cardiac transplantation, as well as cardiomyopathies. Furthermore, response to therapeutic intervention can be monitored using metabolic imaging. Analysis of metabolic data in the past has been limited, focusing primarily on isolated metabolites. Models of myocardial metabolism, however, such as the oxygen transport and cellular energetics model and constraint-based metabolic network modeling, offer opportunities for evaluation interactions between greater numbers of metabolites in the heart. In this review, the roles of metabolic myocardial imaging and analysis of metabolic data using modeling methods for expanding our understanding of cardiac pathology are discussed

Improved Working Memory but No Effect on Striatal Vesicular Monoamine Transporter Type 2 after Omega-3 Polyunsaturated Fatty Acid Supplementation

Studies in rodents indicate that diets deficient in omega-3 polyunsaturated fatty acids (n-3 PUFA) lower dopamine neurotransmission as measured by striatal vesicular monoamine transporter type 2 (VMAT2) density and amphetamine-induced dopamine release. This suggests that dietary supplementation with fish oil might increase VMAT2 availability, enhance dopamine storage and release, and improve dopamine-dependent cognitive functions such as working memory. To investigate this mechanism in humans, positron emission tomography (PET) was used to measure VMAT2 availability pre- and post-supplementation of n-3 PUFA in healthy individuals. Healthy young adult subjects were scanned with PET using [11C]-(+)-α-dihydrotetrabenzine (DTBZ) before and after six months of n-3 PUFA supplementation (Lovaza, 2 g/day containing docosahexaenonic acid, DHA 750 mg/d and eicosapentaenoic acid, EPA 930 mg/d). In addition, subjects underwent a working memory task (n-back) and red blood cell membrane (RBC) fatty acid composition analysis pre- and post-supplementation. RBC analysis showed a significant increase in both DHA and EPA post-supplementation. In contrast, no significant change in [11C]DTBZ binding potential (BPND) in striatum and its subdivisions were observed after supplementation with n-3 PUFA. No correlation was evident between n-3 PUFA induced change in RBC DHA or EPA levels and change in [11C]DTBZ BPND in striatal subdivisions. However, pre-supplementation RBC DHA levels was predictive of baseline performance (i.e., adjusted hit rate, AHR on 3-back) on the n-back task (y = 0.19+0.07, r2 = 0.55, p = 0.009). In addition, subjects AHR performance improved on 3-back post-supplementation (pre 0.65±0.27, post 0.80±0.15, p = 0.04). The correlation between n-back performance, and DHA levels are consistent with reports in which higher DHA levels is related to improved cognitive performance. However, the lack of change in [11C]DBTZ BPND indicates that striatal VMAT2 regulation is not the mechanism of action by which n-3 PUFA improves cognitive performance. © 2012 Narendran et al

4-D Tomographic Inference: Application to SPECT and MR-driven PET

Emission tomographic imaging is framed in the Bayesian and information theoretic framework. The first part of the thesis is inspired by the new possibilities offered by PET-MR systems, formulating models and algorithms for 4-D tomography and for the integration of information from multiple imaging modalities. The second part of the thesis extends the models described in the first part, focusing on the imaging hardware. Three key aspects for the design of new imaging systems are investigated: criteria and efficient algorithms for the optimisation and real-time adaptation of the parameters of the imaging hardware; learning the characteristics of the imaging hardware; exploiting the rich information provided by depthof- interaction (DOI) and energy resolving devices. The document concludes with the description of the NiftyRec software toolkit, developed to enable 4-D multi-modal tomographic inference

Theranostics: New Era in Nuclear Medicine and Radiopharmaceuticals

Malignancy and many inflammatory diseases have become a major concern for mankind over the years. The conventional therapy of these diseases lacks the effectiveness of the better diagnosis and targeted treatment of these diseases, but nuclear medicine can be regarded as a savior in the current scenario. Over the years, radioactivity of radioisotopes has been employed for treatment of many diseases. Nuclear medicines came up with radiopharmaceuticals that impart the ability to destroy specific diseased cells with high-energy-emitting radionuclides. Moreover, the emergence of theranostics, which is a combination of single drug used both for diagnostic as well as therapeutic purpose, has added a new feather in the field of nuclear medicines for providing a specific and personalized treatment to the patient. The current chapter discusses about techniques used for imaging of these radionuclides for better therapy and diagnosis of the root cause of the concerned disease by positron emission tomography (PET)/CT and single photon emission computed tomography (SPECT)/CT as well as the advantages and disadvantages associated with them. It also describes about applications of theranostics and nuclear imaging in cancer treatment and their future perspective

Evaluation of [67Ga]-insulin for insulin receptor imaging

BACKGROUND: Radiolabelled human recombinant insulin can be used for the imaging of insulin receptors in some tumours where FDG has natural uptake and diminishes the value of its imaging. MATERIAL AND METHODS: Insulin was successively labelled with [67 Ga]-gallium chloride after conjugation with freshly prepared cyclic DTPA-dianhydride (HPLC radiochemical purity assay > 96%) followed by biodistribution studies in normal rats, white blood cell labelling and preliminary SPECT studies. RESULTS: In vitro studies demonstrated the retention of radiolabelled insulin receptor affinity using freshly prepared human white blood cells at different blood sugar conditions. Preliminary in vivo studies in a normal rat model was performed to determine the biodistribution of the radioimmunoconjugate at up to 44 h. SPECT images revealed high uptake of the liver. CONCLUSION: Radiolabelled insulin is stable enough to be used in biological studies in order to image insulin receptors in diabetic conditions as well as possible tumour imaging applications. The data was consistent with other radiolabelled insulin studies

Focal Spot, Spring 1993

https://digitalcommons.wustl.edu/focal_spot_archives/1063/thumbnail.jp

Development of Polymer Peptide Conjugates for Enhanced Pancreatic Cancer Imaging

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US with very poor prognosis. All clinically available biomarkers and diagnostic tools either fail to detect early stage PDAC or suffer from low specificity and sensitivity. There is an urgent need for diagnostic agents with greater efficacy for PDAC detection and staging. Nanomaterials such as N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymers can effectively target tumors, and offer novel opportunities for the development of effective diagnostic agents for cancer. However, a major problem of many nanomaterials-based diagnostics is their opsonization and sequestration by the mononuclear phagocyte system (MPS), leading to substantial accumulation in MPS tissues such as the liver and spleen. This MPS accumulation in non-target tissues can hinder identification of resident or nearby metastatic malignant lesions thereby decreasing the diagnostic efficacy. In this thesis, we focused on developing new approaches in which radiolabeled HPMA copolymers can be synthetically modified to significantly reduce the MPS accumulation and/or to increase the tumor accumulation, thereby enhancing the diagnostic and/or radiotherapeutic efficacy of the agents. First, we evaluated the effectiveness of incorporating metabolic active linkers into HPMA copolymers to decrease the radioactivity retention in the liver and spleen in pancreatic tumor xenograft mice. We demonstrated that 177Lu-labeled HPMA copolymers conjugated with cathepsin B/S cleavable peptide linkers exhibited significant long-term reduction in hepatic and splenic radioactivity accumulation as compared to the non-cleavable control. Next we conjugated a 109 kDa HPMA copolymer with three different cathepsin S cleavable linkers and evaluated the structure-activity relationship with regard to the lengths of the linking groups on the in vitro and in vivo efficacy of 177Lu-labeled cathepsin S cleavable HPMA copolymers. Biodistribution results showed that the 177Lu-labeled HPMA copolymer with the shortest length linker had a significant enhancement in the tumor-to-non-target ratios, which was also confirmed by SPECT/CT imaging. Finally, the potential of active tumor targeting for PDAC was evaluated using a plectin-1 targeted peptide (PTP) conjugated HPMA copolymer on pancreatic cancer cells in vitro. Unfortunately, we found that incorporation of the PTP into the HPMA copolymer diminished the binding of the peptide, possibly due to steric hindrance. Overall, our 177Lu-labeled cathepsin cleavable HPMA copolymer showed decreased MPS tissue accumulation and significant improvement in tumor-to-non-target organ ratio, and was successfully applied to SPECT/CT imaging of pancreatic tumors in a xenograft mouse model