Global progress in peptide radiopharmaceutical research and China's opportunities / 药学学报

Radiopharmaceutical is an essential component of nuclear medicine and molecular imaging, as well as a key component of precision medicine. The United States Food and Drug Administration (FDA) has recently approved the marketing of several peptide-based radiopharmaceuticals, sparking a global trend of research in this area and propelling nuclear medicine into the precision theranostic era. This has created a new wave of technological competition in the field of nuclear medicine. It is the responsibility of Chinese scientists in the radiopharmaceutical field to capitalize on this opportunity, leverage the momentum, and strengthen their independent innovation capability in order to stay ahead in the future global nuclear science and technology competition. This review provides an overview of the remarkable progress made in the research, development, and translation of global peptide-based radiopharmaceuticals. It examines the advantages of peptide-based radiopharmaceuticals and outlines the current hot targets and progress in drug development in this field. Additionally, it proposes six opportunities for China to overtake others in the field of peptide-based radiopharmaceuticals and achieve technological self-reliance, based on interdisciplinary collaboration and independent innovation. Lastly, the future prospect of peptide-based radiopharmaceuticals is discussed.

Multimodality Imaging in Patients with Secondary Hypertension: With a Focus on Appropriate Imaging Approaches Depending on the Etiologies

Although the causes of hypertension are usually unknown, about 10% of the cases occur secondary to specific etiologies, which are often treatable. Common categories of secondary hypertension include renal parenchymal disease, renovascular stenosis, vascular and endocrinologic disorders. For diseases involving the renal parenchyma and adrenal glands, ultrasonography (US), computed tomography (CT) or magnetic resonance (MR) imaging is recommended. For renovascular stenosis and vascular disorders, Doppler US, conventional or noninvasive (CT or MR) angiography is an appropriate modality. Nuclear imaging can be useful in the differential diagnosis of endocrine causes. Radiologists should understand the role of each imaging modality and its typical findings in various causes of secondary hypertension. This article focuses on appropriate imaging approaches in accordance with the categorized etiologies leading to hypertension.

Combination of contrast-enhanced cardiac MR and nuclear myocardial imaging in evaluation of myocardial viability in ischemic cardiomyopathy / 中华放射学杂志

Objective To explore the imaging characteristics and the complementarity of contrast?enhanced cardiac magnetic resonance CMR and nuclear myocardial perfusion/metabolic imaging in the evaluation of myocardial viability in patients with ischemic cardiomyopathy. Methods A total of 111 patients with diagnosed coronary artery disease and left ventricular dysfunction were retrospectively enrolled in this study. All patients underwent CMR and nuclear myocardial imaging within 1 month. Cine CMR was employed to evaluate cardiac function and wall motion. Contrast?enhanced CMR and myocardial perfusion/metabolic images were quantitatively assessed using a standard 17-segment and 5-score system. Dysfunctional segments were classified as viable or non?viable based on contrast?enhanced CMR and myocardial perfusion/metabolic imaging, respectively. No enhancement or sub?endocardial enhancement was defined as viable, while transmural enhancement was defined as non?viable. Severely matched perfusion/metabolism defects on nuclear imaging were assigned as non?viable while other patterns were considered as viable. Kappa index was calculated to evaluate the diagnostic concordance in assessing myocardial viability between contrast?enhanced CMR and myocardial perfusion/metabolic imaging. Results Among 1 887 segments in 111 patients, 80.3%(1 516/1 887) were dysfunctional. Of them, 63.3%(959/1 516) were viable and 36.7%(557/1 516) were non?viable on contrast?enhanced CMR, while 79.7%(1 208/1 516) were viable and 20.3%(308/1 516) were non?viable on nuclear myocardial imaging. The two modalities had a moderate concordance (Kappa=0.46,P<0.01). In segments with normal perfusion and metabolism, 73.9% (431/583) had various extent of enhancement but most of them(84.2%, 363/431) were subendocardial. On the other hand, 21.0%(117/557) segments with transmural enhancement had hibernating myocardium on nuclear imaging. Conclusions Contrast?enhanced CMR and nuclear myocardial imaging have a moderate concordance in the evaluation of myocardial viability in ischemic cardiomyopathy. Combination of the two modalities is expected to improve the diagnostic accuracy in assessing myocardial viability.

MicroSPECT and MicroPET Imaging of Small Animals for Drug Development

The process of drug discovery and development requires substantial resources and time. The drug industry has tried to reduce costs by conducting appropriate animal studies together with molecular biological and genetic analyses. Basic science research has been limited to in vitro studies of cellular processes and ex vivo tissue examination using suitable animal models of disease. However, in the past two decades new technologies have been developed that permit the imaging of live animals using radiotracer emission, X-rays, magnetic resonance signals, fluorescence, and bioluminescence. The main objective of this review is to provide an overview of small animal molecular imaging, with a focus on nuclear imaging (single photon emission computed tomography and positron emission tomography). These technologies permit visualization of toxicodynamics as well as toxicity to specific organs by directly monitoring drug accumulation and assessing physiological and/or molecular alterations. Nuclear imaging technology has great potential for improving the efficiency of the drug development process.

Nuclear Imaging of Differentiated Thyroid Cancer: Current Status and Future Perspective / 대한갑상선학회지

Nuclear imaging studies have been used for individualized treatment planning, and to optimize management in patients with differentiated thyroid cancer (DTC). Nuclear imaging studies demonstrate whole body distribution of radioactive tracer and are complementary to radiological studies as they give functional information. Recently, hybrid imaging modalities such as single photon emission computed tomography (CT) with integrated CT and positron emission tomography with integrated CT allow the rapid and efficient fusion of functional and anatomical images, and provide diagnostic information that influence management decision in patients with DTC. This article reviewed nuclear imaging studies and hybrid imaging modalities used in patients with DTC, and future perspectives of functional molecular imaging of the thyroid cancer.

Psycological and physiological responses to stress: a review based on results from PET and MRI studies

A new application for the nuclear imaging techniques is the study of organic responses to stress. Neuroimaging techniques allow the assessment of brain activation changes in association with the metabolic responses to stress. In this paper, a review of general effects of the stress on organic activity is made, emphasizing important advances introduced by studies using PET and fMRI. The importance of the hypothalamus-pituitary-adrenal axis to onset the adequate psychical and organic responses to sustain the homeostasis during the stress is discussed, as well as the possibility of traumatic stressing experiences have negative effects on the brain.

Uma nova aplicação para as técnicas de imagem nuclear é o estudo de respostas orgânicas ao estresse. Técnicas de neuroimagem permitem observar as mudanças da ativação cerebral associadas às respostas metabólicas ao estresse. Neste artigo, uma revisão dos efeitos do estresse sobre a atividade orgânica é feita, enfatizando importantes avanços introduzidos por estudos realizados com PET e fMRI. A importância do eixo hipotálamo-hipófise-adrenal para o disparo das respostas orgânicas e psíquicas para a manutenção da homeostasia durante o estresse é discutida, bem como a possibilidade de experiências estressantes traumáticas exercerem efeitos negativos sobre o cérebro.

Molecular Nuclear Imaging of Angiogenesis / 대한핵의학회잡지

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 exciting new discipline that deals with imaging of disease on a cellular or genetic level. Angiogenesis imaging is 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 alpha v beta3 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.

Nuclear Imaging Evaluation of Galactosylation of Chitosan / 대한핵의학회잡지

PURPOSE: Chitosan has been studied as a non-viral gene delivery vector, drug delivery carrier, metal chelater, food additive, and radiopharmaceutical, among other things. Recently, galactose-graft chitosan was studied as a non-viral gene and drug delivery vector to target hepatocytes. The aim of this study was to investigate the usefulness of nuclear imaging for in vivo evaluation of targeting the hepatocyte by galactose grafting. METHODS AND MATERIALS: Galactosyl methylated chitosan (GMC) was produced by methylation to lactobionic acid coupled chitosan. Cytotoxicity of 99mTc-GMC was determined by MTT assay. Rabbits were injected via their auricular vein with 99mTc-GMC and 99mTc-methylated chitosan (MC), the latter of which does not contain a galactose group, and images were acquired with a gamma camera equipped with a parallel hole collimator. The composition of the galactose group in galactosylated chitosan (GC), as well as the tri-, di-, or mono-methylation of GMC, was confirmed by NMR spectroscopy. RESULTS: The results of MTT assay indicated that 99mTc-GMC was non-toxic. 99mTc-GMC specifically accumulated in the liver within 10 minutes of injection and maintained high hepatic uptake. In contrast, 99mTc-MC showed faint liver uptake. 99mTc-GMC scintigraphy of rabbits showed that the galactose ligand principally targeted the liver while the chitosan functionalities led to excretion through the urinary system. CONCLUSION: Bioconjugation with a specific ligand endows some degree of targetability to an administered molecule or drug, as in the case of galactose for hepatocyte in vivo, and evaluating said targetabililty is a clear example of the great benefit proffered by nuclear imaging.

Distribution of ~(125)Iodine-labeled Interleukin-2 and its relation to insulitis in NOD mice / 中国糖尿病杂志

Objective To evaluate the feasibility of ~ 125 Iodine -labeled IL-2 scintigraphic methods for the imaging of lymphocyte infiltration of the Langerhans′ islets. Methods ~ 125 I-IL2 was injected intravenously to pre-diabetic female NOD mice (aged 16-17 weeks)and female Balb/c mice as control. Animals were sacrificed at different time points and the radioactivity in different organs was measured.~ 131 I-IL-2 was injected iv to 3 pre-diabetic female NOD mice, and pancreas was imaged through SPECT after 30 minutes injection. Results The mean radio activities in the pancreas of NOD mice were significantly higher as compared to those of Balb/c mice at time points from 30 to 120 minutes (P

Molecular imaging probes for integrin ?_V?_3 / 中国癌症杂志

Integrin ?V?3, one of the major members of the integrin family, plays a pivotal role in tumor angiogenesis because it mediates the cell-extracellular matrix and cell to cell adhesion as well as controls cells proliferation, differentiation, cellular modality and motility.Due to restricted high-expressions in tumors, integrin ?V?3, is considered a suitable targeting receptor for tumor diagnosis.In the past decade, several molecular imaging tracers for integrin ?V?3, have been used to noninvasively visualize its expression in tumor tissues and angiogenic blood vessels through the usage of nuclear imaging, nuclear magnetic resonance imaging, ultrasound, and optical imaging.Noninvasive detection of integrin ?V?3, expression can potentially be used for tumor diagnosis and prognosis.The current imaging probes used to target integrin ?V?3, through usage of different technologies are briefly recapitulated in this review.