[en] Angiogenesis, the formation of new capillaries from existing vessels, increases oxygenation and nutrient supply to ischemic tissue and allows tumor growth and metastasis. As such, angiogenisis targeting provides a novel approach for cancer treatment with easier drug delivery and less drug resistance. Therapeutic anti-angiogenesis has shown impressive effects in animal tumor models and are now entering clinical trials. However, the successful clinical introduction of this new therapeutic approach requires diagnostic tools that can reliably measure angiogenesis in a noninvasive and repetitive manner. Molecular imaging is emerging as an important area for molecular imaging research, and the use of radiotracers offers a particularly promising technique for its development. While current perfusion and metabolism radiotracers can provide useful information related to tissue vascularity, recent endeavors are focused on the development of novel radioprobes that specifically and directly target angiogenic vessels. Presently available probes include RGD sequence containing peptides that target α_v β₃ integrin, endothelial growth factors such as VEGF or FGF, metalloproteinase inhibitors, and specific antiangiogenic drugs. It is now clear that nuclear medicine techniques have a remarkable potential for angiogenesis imaging, and efforts are currently continuing to develop new radioprobes with superior imaging properties. With future identification of novel targets, design of better probes, and improvements in instrumentation, radiotracer angiogenesis imaging promises to play an increasingly important role in the diagnostic evaluation and treatment of cancer and other angiogenesis related diseases

[en] Nuclear medicine has traditionally contributed to molecular oncology by allowing noninvasive monitoring of tumor metabolism, growth and genetic changes, thereby providing a basis for appropriate biology-based treatment planning. However, NM techniques are now being applied as an active therapeutic tool in novel molecular approaches for cancer treatment. Such areas include research on cancer therapy with radiolabeled ligands or oligonucleotides, and utilization of synergism between NM radiotherapy and gene transfer techniques. Here we will focus on novel aspects of nuclear medicine therapy

[en] In addition to the well-established use of positron emission tomography (PET) in clinical oncology, novel roles for PET are rapidly emerging in the field of gene therapy. Methods for controlled gene delivery to living bodies, made available through advances in molecular biology, are currently being employed in animals for reasearch purposes and in humans to treat diseases such as cancer. Although gene therapy is still in its early developmental stage, it is perceived that many serious illnesses could be treated successfully by the use of therapeutic gene delivery. A major challenge for the widespread use of human gene therapy is to achieve a controlled and effective delivery of foreign genes to target cells and subsequently, adequate levels of expression. As such, the availability of noninvasive imaging methods to accurately assess the location, duration, and level of transgene expression is critical for optimizing gene therapy strategies. Current endeavors to achieve this goal include methods that utilize magnetic resonance imaging, optical imaging, and nuclear imaging techniques. As for PET, reporter systems that utilize gene encoding enzymes that accumulate postion labeled substrates and those transcribing surface receptors that bind specific positron labeled ligands have been successfully developed. More recent advances in this area include improved reporter gene constructs and radiotracers, introduction of potential strategies to monitor endogenous gene expression, and human pilot studies evaluating the distribution and safety of reporter PET tracers. The remarkably rapid progress occuring in gene imaging technology indicates its importance and wide range of application. As such, gene imaging is likely to become a major and exciting new area for future application of PET technology

[en] The rapid progress of molecular genetic methods over the past two decades has necessitated the development of methods to detect and quantify genetic activity within living bodies. Reporter genes provide a rapid and convenient tool to monitor gene expression by yielding a readily measurable phenotype upon expression when introduced into a biological system. Conventional reporter systems, however, are limited in their usefulness for in vivo experimjents or human gene therapy because of its invasive nature which requires cell damage before assays can be performed. This offers an unique opportunity for nuclear imaging techniques to develope a novel method for imaging both the location and amount of gene expression noninvasively. Current developments to achieve this goal rely on utilizing either reporter enzymes that accumulate radiolabeled substrates or reporter receptors that bind specific radioligands. This overview includes a brief introduction to the background for such research, a summary of published fresults, and an outlook for future directions

[en] Molecular imaging strives to visualize processes in living subjects at the molecular level. Monitoring biochemical processes at this level will allow us to directly track biological processes and signaling events that lead to pathophysiological abnormalities, and help make personalized medicine a reality by allowing evaluation of therapeutic efficacies on an individual basis. Although most molecular imaging techniques emerged from the field of oncology, they have now gradually gained acceptance by the cardiovascular community. Hence, the availability of dedicated high-resolution small animal imaging systems and specific targeting imaging probes is now enhancing our understanding of cardiovascular diseases and expediting the development of newer therapies. Examples include imaging approaches to evaluate and track the progress of recent genetic and cellular therapies for treatment of myocardial ischemia. Other areas include in vivo monitoring of such key molecular processes as angiogenesis and apoptosis. Cardiovascular molecular imaging is already an important research tool in preclinical experiments. The challenge that lies ahead is to implement these techniques into the clinics so that they may help fulfill the promise of molecular therapies and personalized medicine, as well as to resolve disappointments and controversies surrounding the field

[en] Radioiodide transport has been extensively and successfully used in the evaluation and management of thyroid disease. The molecular characterization of the sodium/iodide symporter (NIS) and cloning of the NIS gene has led to the recent expansion of the use of radioiodide to cancers of the breast and other nonthyroidal tissues exogenously transduced with the NIS gene. More recently, discoveries regarding the functional analysis and regulatory processes of the NIS molecule are opening up exciting opportunities for new research and applications for NIS and radioiodide. The success of NIS based cancer therapy is dependent on achievement of maximal radioiodide transport sufficient to allow delivery of effective radiation doses. This in turn relies on high transcription rates of the NIS gene. However, newer discoveries indicate that nontranscriptional processes that regulate NIS trafficking to cell membrane are also critical determinants of radioiodide uptake. In this review, molecular mechanisms that underlie regulation of NIS transcription and stimuli that augment membrane trafficking and functional activation of NIS molecules will be discussed. A better understanding of how the expression and cell surface targeting of NIS proteins is controlled will hopefully aid in optimizing NIS gene based cancer treatment as well as NIS based reporter-gene imaging strategies

[en] Patterns of abnormality in regional cerebral perfusion and its relation to clinical severity was evaluated with 32 head injury patients using '9^9mTc-HMPAO single photon emission tomography (SPECT). The findings were compared with computed tomography (CT) done within 48 hours of each SPECT study. The initial SPECT study was done within 7 days of injury in 16 cases, between 1 week and 2 months in 12, and after over 2 months in 4. Nineteen of the patients underwent follow up SPECT and CT after a mean interval of 1 to 2 months. The initial SPECT showed abnormalities in 96% (31/32) of the patients while CT showed abnormal findings in only 81% (26/32). There were a total of 54 supratentorial SPECT lesions in all. Ninety percent (49/54) of these were of regional hypoperfusion, while 5 lesions showed focal hyperperfusion. The lesions were most often localized in the frontal and temporal lobes. Fifty five percent (30/54) were areas not detected as a lesion on CT. Cerebellar diaschisis was observed in 50% (16/32) of the patients. The degree of perfusion abnormality was quantified by the product of differential activity and a size factor. Correlation between the degree of perfusion abnormality and the clinical severity (Glasgow coma scale) failed to show statistical significance (p=0.053). The amount of change in the degree of perfusion abnormality on follow up SPECT was compared to the amount of change in clinical severity. Perfusion abnormality showed a tendency to improve in most patients, and the degree of improvement showed significant correlation with the amount of clinical improvement (p<0.01).

[en] While indirect targeting strategies using reporter-genes are taking center stage in current molecular imaging research, another vital strategy has long involved direct imaging of specific receptors using radiolabeled ligands. Recently, there is renewal of immense interest in this area with particular attention to the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein critically involved in the regulation of many cellular functions and malignancies. Recently, two novel classes of EGFR-targeting anticancer drugs have entered clinical trials with great expectations. These are monoclonal antibodies such as cetuximab that target the extracellular domain, and small molecule tyrosine kinase inhibitors such as gefitinib (Iressa) and erlotinib (Tarceva) that target the catalytic domain of the receptor. However, early results have showed disappointing survival benefits, disclosing a major challenge for this therapeutic strategy; namely, the need to identify tumors that are most likely to respond to the agents. To address this important clinical issue, several noninvasive imaging techniques are under investigation including radiolabeled probes based on small molecule tyrosine kinase inhibitors, anti-EGFR antibodies, and EGF peptides. This review describes the current status, limitations, and future prospects in the development of radiotracer methods for EGFR imaging

[en] Introduction: High-dose ¹⁸F-FDG can provide targeted nuclear therapy of cancer. Endothelial cell injury is a key determinant of tumor response to radiotherapy. Here, we tested the hypothesis that activation of endothelial cell glycolytic metabolism with nitric oxide can enhance the therapeutic effect of high-dose ¹⁸F-FDG. Methods: Calf pulmonary artery endothelial (CPAE) cells were treated with graded doses of ¹⁸F-FDG. Glycolysis was stimulated by 24 h of exposure to the nitric oxide donor, sodium nitroprusside (SNP). Cell viability was assessed by MTT and clonogenic assays. Apoptosis was evaluated by ELISA of cytosolic DNA fragments and Western blots of cleaved caspase-3. Results: SNP stimulation (0.1 and 1 mM) augmented CPAE cell ¹⁸F-FDG uptake to 2.6- and 4.6-fold of controls without adverse effects. Treatment with 333 μCi/ml ¹⁸F-FDG alone reduced viable cell number to 35.4% of controls by Day 3. Combining 0.1 mM SNP stimulation significantly enhanced the killing effect, reducing cell numbers to 19.2% and 39.2% of controls by 333 and 167 μCi/ml of ¹⁸F-FDG, respectively. ¹⁸F-FDG also suppressed clonogenic survival to 80.8% and 43.2% of controls by 83 and 167 μCi/ml, which was again intensified by SNP to 59.7% and 21.1% of controls. The cytotoxic effect of ¹⁸F-FDG was attributed to induction of apoptosis as shown by increased cytosolic fragmented DNA and cleaved caspase-3 levels (26.4% and 30.7% increases by 167 μCi/ml). Combining SNP stimulation significantly increased both of these levels to 1.8-fold of control cells. Conclusion: High-dose ¹⁸F-FDG combined with nitric oxide-stimulated glycolysis is an effective method to inhibit endothelial cell survival and promote apoptosis. These results suggest a potential role of this strategy for targeted radiotherapy of angiogenic vasculature.

[en] Since its introduction 20 years ago, nuclear cardiology in the Republic of Korea has grown impressively and is now widely used as a noninvasive procedure in the diagnosis and functional evaluation of various types of heart diseases. All of the classes of procedures, that is, first-pass radionuclide cardioangiography, gated blood pool scan, myocardial perfusion imaging, and myocardial infarct imaging, are being employed frequently and have been the subject of numerous studies. First-pass radionuclide ventriculography is being used in the detection and quantification of intracardiac shunts, the evaluation of chamber size, function, or cardiopulmonary dynamics in various disease states. With gated blood pool scans, several parameters of cardiac function are being measured in a variety of conditions including coronary heart disease. Quantifications of regurgitations are also being done. Both thallium-201 and technetium-99m pyrophosphate are being used in the diagnosis of coronary artery disease. Besides clinical imaging, active research in the field of nuclear cardiology has also been taking place in the Republic of Korea. Examples include investigations on new imaging agents such as ¹¹¹In-antimyosin monoclonal antibody and hexakis technetium(I) cations, or instrumental developments such as the nuclear stethoscope. Despite such noteworthy accomplishments, however, there have also been some obstacles to further developments in the Republic of Korea, such as the unavailability of a cyclotron. Nevertheless, considering the rate of expansion these procedures are showing and the effort we are putting into further development, the future for nuclear cardiology in the Republic of Korea appears quite promising and may become an example for other developing countries. (author). 28 refs, 5 figs, 2 tabs