99mTc-HYNIC/Cy7-Fab(Bevacizumab): su empleo como agente de imagen en mieloma múltiple / 99mTc-HYNIC/Cy7-Fab(Bevacizumab): its use as an imaging agent in Multiple Myeloma / 99mTc-HYNIC/Cy7-Fab (Bevacizumab): seu uso como agente de imagem em mieloma múltiplo

Introducción: el mieloma múltiple es un trastorno hematológico maligno y el segundo cáncer de la sangre más frecuente. El proceso de la angiogénesis tumoral es fundamental para el crecimiento y metástasis de muchos tipos de tumores, incluido en mieloma múltiple. Se sabe que la sobreexpresión del factor de crecimiento endothelial vascular se encuentra asociado a un mal pronóstico en esta patología, representando un blanco clave para la terapia anti-angiogénica en mieloma múltiple. El anticuerpo monoclonal Bevacizumab es capaz de unirse con gran afinidad al factor de crecimiento endothelial vascular bloqueando su acción. Objetivo: evaluar el Fab(Bevacizumab) marcado con 99mTc o Cy7 como potenciales agentes de imagen moleculares de la expresión de factor de crecimiento endothelial vascular en mieloma múltiple. Material y métodos: la expresión de factor de crecimiento endothelial vascular fue analizada mediante citometría de flujo en la línea celular huaman de mieloma múltiple, la MM1S. Fab(Bevacizumab) fue producido mediante digestión de Bevacizumab con papaína, conjugado a NHS-HYNIC-Tfa y radiomarcado con 99mTc. Se realizaron estudios de biodistribución y de tomografía computarizada por emisión del fotón simple. A su vez, Fab(Bevacizumab) fue marcado con Cy7 para obtener imágenes de fluorescencia in vivo hasta 96 horas. Resultados: el análisis por citometría de flujo en la línea celular MM1S reveló que la expresión de factor de crecimiento endothelial vascular es predominantemente intracelular. Los estudios de biodistribución y SPECT/CT del complejo 99mTc-HYNIC-Fab(Bevacizumab) mostraron una rápida eliminación sanguínea y una significativa captación a nivel renal y tumoral. Las imágenes por fluorescencia empleando Cy7-Fab(Bevacizumab) permitieron la visualización tumoral hasta 96 h p.i. Conclusiones: logramos visualizar la expresión de factor de crecimiento endothelial vascular in vivo en mieloma múltiple mediante el empleo del fragmento Fab del anticuerpo anti-VEGF (Bevacizumab) marcado con 99mTc y Cy7. Estos nuevos agentes de imagen molecular podrían ser empleados potencialmente en el ámbito clínico para la estadificación y el seguimiento de pacientes con mieloma múltiple, mediante la visualización radioactiva in vivo de la expresión de factor de crecimiento endothelial vascular en todo el cuerpo. La imagen óptica de estos trazadores mejoraría el muestreo tumoral y podría guiar la extirpación quirúrgica.

Introduction: Multiple myeloma is a hematologic malignancy and the second most common blood cancer. The process of tumor angiogenesis is central to the growth and metastasis of many types of tumors, including multiple myeloma. Overexpression of vascular endothelial growth factor is known to be associated with poor prognosis in this pathology, representing a key target for anti-angiogenic therapy in multiple myeloma. The monoclonal antibody Bevacizumab is able to bind with high affinity to vascular endothelial growth factor blocking its action. Objective: to evaluate 99mTc- or Cy7-labeled Fab(Bevacizumab) as potential molecular imaging agents of vascular endothelial growth factor expression in multiple myeloma. Methods: Vascular endothelial growth factor expression was analyzed by flow cytometry in the multiple myeloma huaman cell line, MM1S. Fab(Bevacizumab) was produced by digestion of Bevacizumab with papain, conjugated to NHS-HYNIC-Tfa and radiolabeled with 99mTc. Biodistribution and single photon emission computed tomography studies were performed. In turn, Fab(Bevacizumab) was labeled with Cy7 to obtain in vivo fluorescence images up to 96 hours. Results: Flow cytometry analysis in the MM1S cell line revealed that vascular endothelial growth factor expression is predominantly intracellular. Biodistribution and SPECT/CT studies of the 99mTc-HYNIC-Fab(Bevacizumab) complex showed rapid blood clearance and significant renal and tumor uptake. Fluorescence imaging using Cy7-Fab(Bevacizumab) allowed tumor visualization up to 96 h p.i. Conclusions: we were able to visualize vascular endothelial growth factor expression in vivo in multiple myeloma using the Fab fragment of the anti-VEGF antibody (Bevacizumab) labeled with 99mTc and Cy7. These new molecular imaging agents could potentially be employed in the clinical setting for staging and monitoring of patients with multiple myeloma by in vivo radioactive visualization of vascular endothelial growth factor expression throughout the body. Optical imaging of these tracers would improve tumor sampling and could guide surgical excision.

Introdução: O mieloma múltiplo é uma malignidade hematológica e o segundo câncer de sangue mais comum. O processo de angiogênese tumoral é fundamental para o crescimento e a metástase de muitos tipos de tumores, incluindo o mieloma múltiplo. Sabe-se que a superexpressão do fator de crescimento endotelial vascular está associada a um prognóstico ruim no mieloma múltiplo, representando um alvo importante para a terapia antiangiogênica no mieloma múltiplo. O anticorpo monoclonal Bevacizumab é capaz de se ligar com alta afinidade ao fator de crescimento endotelial vascular e bloquear sua ação. Objetivo: avaliar o Fab(Bevacizumab) marcado com 99mTc ou Cy7 como possíveis agentes de imagem molecular da expressão do fator de crescimento endotelial vascular no mieloma múltiplo. Métodos: A expressão do fator de crescimento endotelial vascular foi analisada por citometria de fluxo na linha celular de mieloma múltiplo MM1S. O Fab(Bevacizumab) foi produzido pela digestão do Bevacizumab com papaína, conjugado com NHS-HYNIC-Tfa e radiomarcado com 99mTc. Foram realizados estudos de biodistribuição e tomografia computadorizada por emissão de fóton único. Por sua vez, o Fab(Bevacizumab) foi marcado com Cy7 para geração de imagens de fluorescência in vivo por até 96 horas. Resultados: A análise de citometria de fluxo na linha celular MM1S revelou que a expressão do fator de crescimento endotelial vascular é predominantemente intracelular. Os estudos de biodistribuição e SPECT/CT do complexo 99mTc-HYNIC-Fab(Bevacizumab) mostraram uma rápida depuração sanguínea e uma captação renal e tumoral significativa. A imagem de fluorescência usando Cy7-Fab(Bevacizumab) permitiu a visualização do tumor até 96 horas p.i. Conclusões: Conseguimos visualizar a expressão do fator de crescimento endotelial vascular in vivo no mieloma múltiplo usando o fragmento Fab do anticorpo anti-VEGF (Bevacizumab) marcado com 99mTc e Cy7. Esses novos agentes de imagem molecular poderiam ser usados no cenário clínico para o estadiamento e o monitoramento de pacientes com mieloma múltiplo, visualizando radioativamente a expressão do fator de crescimento endotelial vascular in vivo em todo o corpo. A geração de imagens ópticas desses traçadores melhoraria a amostragem do tumor e poderia orientar a excisão cirúrgica.

Research Progress of Targeted Ultrasound Contrast Agent BR55 / 中国医学科学院学报

BR55 is an ultrasound contrast agent targeting vascular endothelial growth factor receptor 2,which can be used to detect tumor neovascularization and improve the diagnostic accuracy.Overseas researchers have used BR55 for human ultrasound molecular imaging,which showed good safety and tolerance.We reviewed the research progress on BR55 applied in the evaluation of tumor neovascularization from the composition,characteristics,animal experiments,and clinical studies of BR55.

Análogos de somatostatina radiomarcados en el acercamiento diagnóstico del síndrome de Sjögren: Imágenes moleculares aportando a los criterios clínicos y paraclínicos hoy conocidos / Radiolabelled somatostatin analogues in the diagnostic approach to Sjögren's syndrome: molecular imaging contributing to the current clinical and para-clinical criteria

RESUMEN El diagnóstico del síndrome de Sjögren se basa en los criterios del consenso americano y europeo (AECG), sin embargo, en muchas oportunidades no se alcanza a detectar el compromiso glandular o extraglandular. Presentamos la evidencia de la utilidad de la gammagrafía con los análogos de somatostatina radiomarcados como prueba novedosa en el acercamiento diagnóstico al compromiso glandular y extraglandular del síndrome de Sjögren.

ABSTRACT Sjögren syndrome is diagnosed using American European Consensus Group (AECG) criteria, although frequently these criteria are not enough to detect the glandular and extra-glandular compromise. Evidence is presented on the use of whole body somatostatin scintigraphy as a novel probe in the diagnostic approach to the glandular and extra-glandular compromise in Sjögren s syndrome.

Evaluation of dentinogenesis inducer biomaterials: an in vivo study

Abstract When exposure of the pulp to external environment occurs, reparative dentinogenesis can be induced by direct pulp capping to maintain pulp tissue vitality and function. These clinical situations require the use of materials that induce dentin repair and, subsequently, formation of a mineralized tissue. Objective: This work aims to assess the effect of tricalcium silicate cements and mineral trioxide aggregate cements, including repairing dentin formation and inflammatory reactions over time after pulp exposure in Wistar rats. Methodology: These two biomaterials were compared with positive control groups (open cavity with pulp tissue exposure) and negative control groups (no intervention). The evaluations were performed in three stages; three, seven and twenty-one days, and consisted of an imaging (nuclear medicine) and histological evaluation (H&E staining, immunohistochemistry and Alizarin Red S). Results: The therapeutic effect of these biomaterials was confirmed. Nuclear medicine evaluation demonstrated that the uptake of 99mTc-Hydroxymethylene diphosphonate (HMDP) showed no significant differences between the different experimental groups and the control, revealing the non-occurrence of differences in the phosphocalcium metabolism. The histological study demonstrated that in mineral trioxide aggregate therapies, the presence of moderate inflammatory infiltration was found after three days, decreasing during follow-ups. The formation of mineralized tissue was only verified at 21 days of follow-up. The tricalcium silicate therapies demonstrated the presence of a slight inflammatory infiltration on the third day, increasing throughout the follow-up. The formation of mineralized tissue was observed in the seventh follow-up day, increasing over time. Conclusions: The mineral trioxide aggregate (WhiteProRoot®MTA) and tricalcium silicate (Biodentine™) present slight and reversible inflammatory signs in the pulp tissue, with the formation of mineralized tissue. However, the exacerbated induction of mineralized tissue formation with the tricalcium silicate biomaterial may lead to the formation of pulp calcifications

Insights into Hypoxia: Non-invasive Assessment through Imaging Modalities and Its Application in Breast Cancer / 한국유방암학회지

Oxygen is crucial to maintain the homeostasis in aerobic cells. Hypoxia is a condition in which cells are deprived of the oxygen supply necessary for their optimum performance. Whereas oxygen deprivation may occur in normal physiological processes, hypoxia is frequently associated with pathological conditions. It has been identified as a stressor in the tumor microenvironment, acting as a key mediator of cancer development. Numerous pathways are activated in hypoxic cells that affect cell signaling and gene regulation to promote the survival of these cells by stimulating angiogenesis, switching cellular metabolism, slowing their growth rate, and preventing apoptosis. The induction of dysregulated metabolism in cancer cells by hypoxia results in aggressive tumor phenotypes that are characterized by rapid progression, treatment resistance, and poor prognosis. A non-invasive assessment of hypoxia-induced metabolic and architectural changes in tumors is advisable to fully improve breast cancer (BC) patient management, by potentially reducing the need for invasive biopsy procedures and evaluating tumor response to treatment. This review provides a comprehensive overview of the molecular changes in breast tumors secondary to hypoxia and the non-invasive imaging alternatives to evaluate oxygen deprivation, with an emphasis on their application in BC and the advantages and limitations of the currently available techniques.

Non-invasive molecular imaging of immune cell dynamics for vaccine research

In order to develop a successful vaccine against deadly diseases with a wide range of antigenic diversity, an in-depth knowledge of the molecules and signaling mechanisms between the vaccine candidates and immune cells is required. Therefore, monitoring vaccine components, such as antigen or adjuvants, and immune cell dynamics at the vaccination site or draining lymph nodes can provide important information to understand more about the vaccine response. This review briefly introduces and describes various non-invasive molecular imaging methods for visualizing immune cell dynamics after vaccination.

Identification of Radioactive Iodine Refractory Differentiated Thyroid Cancer / 전남의대학술지

Most differentiated thyroid cancer (DTC) patients have an excellent prognosis. However, about one-third of DTC patients with recurrent or metastatic disease lose the hallmark of specific iodine uptake initially or gradually and acquire radioactive iodine-refractory DTC (RAIR-DTC) with poor prognosis. Due to the potentially severe complications from unnecessarily repeated RAI therapy and encouraging progress of multiple targeted drugs for advanced RAIR-DTC patients, it has become crucial to identify RAIR-DTC early. In this review, we focus on the progress and controversies regarding the defining of RAIR-DTC, further with subsistent approaches and promising molecular nuclear medicine imaging in identifying RAIR-DTC, which may shed light on the proper management methodsof such patients.

Understanding Vulnerable Plaques: Current Status and Future Directions

The main cause of acute myocardial infarction is plaque rupture accompanied by superimposed coronary thrombosis. Thin-cap fibroatheromas (TCFAs) have been suggested as a type of lesion with a vulnerability that can cause plaque rupture. However, not only the existence of a TCFA but also the fine and complex interactions of other anatomical and hemodynamic factors, such as microcalcification in the fibrous cap, cholesterol crystal-induced inflammasome activation, the apoptosis of intraplaque macrophages, and endothelial shear stress distribution should precede a clinical event caused by plaque rupture. Recent studies are being conducted to identify these mechanisms through molecular imaging and hemodynamic assessment using computational fluid dynamics, which will result in better clinical results through selective coronary interventions.

Updates in molecular imaging techniques

No abstract available.

Targeted Near-Infrared Fluorescence Imaging for Regenerative Medicine

BACKGROUND: Advances in tissue engineering and regenerative medicine over the last three decades have made great progress in the development of diagnostic and therapeutic methodologies for damaged tissues. However, regenerative medicine is still not the first line of treatment for patients due to limited understanding of the tissue regeneration process. Therefore, it is prerequisite to develop molecular imaging strategies combined with appropriate contrast agents to validate the therapeutic progress of damaged tissues. METHODS: The goal of this review is to discuss the progress in the development of near-infrared (NIR) contrast agents and their biomedical applications for labeling cells and scaffolds, as well as monitoring the treatment progress of native tissue in living organisms. We also discuss the design consideration of NIR contrast agents for tissue engineering and regenerative medicine in terms of their physicochemical and optical properties. RESULTS: The use of NIR imaging system and targeted contrast agents can provide high-resolution and high sensitivity imaging to track/monitor the in vivo fate of administered cells, the degradation rate of implanted scaffolds, and the tissue growth and integration of surrounding cells during the therapeutic period. CONCLUSION: NIR fluorescence imaging techniques combined with targeted contrast agents can play a significant role in regenerative medicine by monitoring the therapeutic efficacy of implanted cells and scaffolds which would enhance the development of cell therapies and promote their successful clinical translations.

Illuminating the Activated Brain: Emerging Activity-Dependent Tools to Capture and Control Functional Neural Circuits / 神经科学通报·英文版

Immediate-early genes (IEGs) have long been used to visualize neural activations induced by sensory and behavioral stimuli. Recent advances in imaging techniques have made it possible to use endogenous IEG signals to visualize and discriminate neural ensembles activated by multiple stimuli, and to map whole-brain-scale neural activation at single-neuron resolution. In addition, a collection of IEG-dependent molecular tools has been developed that can be used to complement the labeling of endogenous IEG genes and, especially, to manipulate activated neural ensembles in order to reveal the circuits and mechanisms underlying different behaviors. Here, we review these techniques and tools in terms of their utility in studying functional neural circuits. In addition, we provide an experimental strategy to measure the signal-to-noise ratio of IEG-dependent molecular tools, for evaluating their suitability for investigating relevant circuits and behaviors.

Molecular Imaging in Breast Cancer / 대한핵의학회잡지

Breast cancer (BC) is themost common cancer among females withmore than 2 million new cases diagnosed worldwide in 2018. Although the prognosis in the majority of cases in the early stages combined with appropriate treatment is positive, there are still about 30% of patients who will develop locoregional diseases and distant metastases. Molecular imaging is very important in the diagnosis, staging, follow-up, and radiotherapy planning. Additionally, it is useful in characterizing lesions, prognosis, and therapy response in BC patients. Nuclear medicine imaging modalities (SPECT and PET) are of indispensable importance in diagnosis (positron emission mammography), staging (sentinel lymph node detection), and follow-up with ¹⁸F-FDG and tumor characterization. Among many available PET tracers, the most commonly used are ¹⁸F-FLT, ¹⁸F-FES, ¹⁸F-FDHT, ⁶⁴Cu DOTA trastuzumab (bevacizumab), ⁶⁸Ga-PSMA, ⁶⁸Ga-RM2 (gastrin-releasing peptide receptor), ¹⁸F-fluorooctreotide (SSTR), and ⁶⁸Ga-TRAP (RGD)-3αvβ3-integrin. Molecular imaging helps in evaluation of tumor heterogeneity, allowing a shift from one-size-fits-all-approach to era of personalized medicine and precision oncology.

Use of Molecular Imaging in Clinical Drug Development: a Systematic Review / 대한핵의학회잡지

BACKGROUND: Molecular imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can provide the crucial pharmacokinetic-pharmacodynamic information of a drug non-invasively at an early stage of clinical drug development. Nevertheless, not much has been known how molecular imaging has been actually used in drug development studies.METHODS: We searched PubMed using such keywords as molecular imaging, PET, SPECT, drug development, and new drug, or any combination of those to select papers in English, published from January 1, 1990, to December 31, 2015. The information about the publication year, therapeutic area of a drug candidate, drug development phase, and imaging modality and utility of imaging were extracted.RESULTS: Of 10,264 papers initially screened, 208 papers met the eligibility criteria. The more recent the publication year, the bigger the number of papers, particularly since 2010. The two major therapeutic areas using molecular imaging to develop drugs were oncology (47.6%) and the central nervous system (CNS, 36.5%), in which efficacy (63.5%) and proof-of-concept through either receptor occupancy (RO) or other than RO (29.7%), respectively, were the primary utility of molecular imaging. PET was used 4.7 times more frequently than SPECT. Molecular imaging was most frequently used in phase I clinical trials (40.8%), whereas it was employed rarely in phase 0 or exploratory IND studies (1.4%).CONCLUSIONS: The present study confirmed the trend that molecular imaging has been more actively employed in recent clinical drug development studies although its adoption was rather slow and rare in phase 0 studies.

Progress of Coordination and Utilization of Zirconium-89 for Positron Emission Tomography (PET) Studies / 대한핵의학회잡지

Radiometals have been commonly used in medical applications, and utilization of such metals continues to be an attractive research area. In particular, a variety of radiometals have been developed and implemented for molecular imaging. For such applications, ⁸⁹Zr has been one of the most interesting radiometals currently used for tumor targeting. Several chemical ligands were developed as ⁸⁹Zr chelators, and new coordinating methods have also been developed more recently. In addition, immunopositron emission tomography (PET) studies using ⁸⁹Zr-labeled monoclonal antibodies have been performed by several scientists. In this review, recent advances to the coordination of ⁸⁹Zr and the utilization of ⁸⁹Zr in PET studies are described.

Current Status of Theranostics in Jordan / 대한핵의학회잡지

Exploring the unknown is one of the key factors that lead to great discoveries in mankind history.With the advances in medicine and the development of new approaches towards patient care, like next-generation sequencing and patient-centered care, the need for treatments tailored to patient through personalized medicine has become more compelling. Theranostics has been introduced as a combination of a diagnostic tool and a therapeutic tool on the same vector for a specific disease, to facilitate personalized medicine. Nuclear medicine has shown the capability of providing a strong platform for this new approach through its arms, molecular imaging, and targeted molecular therapies. Though the prototype of theranostics has been practiced in Jordan since decades in the field of diagnosis and treatment of well-differentiated thyroid cancer, recently, the King Hussein Cancer Center (KHCC), a leading and comprehensive cancer center in Jordan and in the Middle East, has leaped forward to introduce the new approaches of theranostics through the nuclear medicine applications. This paper sheds the light on the most important aspects of this new theranostics practice in Jordan such as peptide receptor radionuclide therapy (PRRT) and prostate-specific membrane antigen (PSMA)–based theranostics.

Progress and Challenges for Live-cell Imaging of Genomic Loci Using CRISPR-based Platforms / 基因组蛋白质组与生物信息学报·英文版

Chromatin conformation, localization, and dynamics are crucial regulators of cellular behaviors. Although fluorescence in situ hybridization-based techniques have been widely utilized for investigating chromatin architectures in healthy and diseased states, the requirement for cell fixation precludes the comprehensive dynamic analysis necessary to fully understand chromatin activities. This has spurred the development and application of a variety of imaging methodologies for visualizing single chromosomal loci in the native cellular context. In this review, we describe currently-available approaches for imaging single genomic loci in cells, with special focus on clustered regularly interspaced short palindromic repeats (CRISPR)-based imaging approaches. In addition, we discuss some of the challenges that limit the application of CRISPR-based genomic imaging approaches, and potential solutions to address these challenges. We anticipate that, with continued refinement of CRISPR-based imaging techniques, significant understanding can be gained to help decipher chromatin activities and their relevance to cellular physiology and pathogenesis.

Consensus of Chinese experts on the application of molecular imaging targeting prostate specific membrane antigen in prostate cancer patients / 中华外科杂志

Recently, prostate cancer has become the most common male urological cancer worldwide. However, it was difficult for the currently widely available imaging modalities to precisely diagnose this disease. With the development of nuclear medical technology, molecular imaging targeting prostate specific membrane antigen has been introduced into China. To promote the standardization of this imaging modality, the experts consensus was published by Chinese Anticancer Association Genitourinary Oncology Committee and recommendations for its application in the diagnosis and treatment of prostate cancer were attached, which would be helpful for doctors who are conducting or preparing for this examination.

Update on Molecular Imaging in Parkinson's Disease / 神经科学通报·英文版

Advances in radionuclide tracers have allowed for more accurate imaging that reflects the actions of numerous neurotransmitters, energy metabolism utilization, inflammation, and pathological protein accumulation. All of these achievements in molecular brain imaging have broadened our understanding of brain function in Parkinson's disease (PD). The implementation of molecular imaging has supported more accurate PD diagnosis as well as assessment of therapeutic outcome and disease progression. Moreover, molecular imaging is well suited for the detection of preclinical or prodromal PD cases. Despite these advances, future frontiers of research in this area will focus on using multi-modalities combining positron emission tomography and magnetic resonance imaging along with causal modeling with complex algorithms.

Deep Learning in Nuclear Medicine and Molecular Imaging: Current Perspectives and Future Directions / 대한핵의학회잡지

Recent advances in deep learning have impacted various scientific and industrial fields. Due to the rapid application of deep learning in biomedical data, molecular imaging has also started to adopt this technique. In this regard, it is expected that deep learning will potentially affect the roles of molecular imaging experts as well as clinical decision making. This review firstly offers a basic overview of deep learning particularly for image data analysis to give knowledge to nuclear medicine physicians and researchers. Because of the unique characteristics and distinctive aims of various types of molecular imaging, deep learning applications can be different from other fields. In this context, the review deals with current perspectives of deep learning in molecular imaging particularly in terms of development of biomarkers. Finally, future challenges of deep learning application for molecular imaging and future roles of experts in molecular imaging will be discussed.

Stem Cell Tracing Through MR Molecular Imaging

Stem cell therapy opens a new window in medicine to overcome several diseases that remain incurable. It appears such diseases as cardiovascular disorders, brain injury, multiple sclerosis, urinary system diseases, cartilage lesions and diabetes are curable with stem cell transplantation. However, some questions related to stem cell therapy have remained unanswered. Stem cell imaging allows approval of appropriated strategies such as selection of the type and dose of stem cell, and also mode of cell delivery before being tested in clinical trials. MRI as a non-invasive imaging modality provides proper conditions for this aim. So far, different contrast agents such as superparamagnetic or paramagnetic nanoparticles, ultrasmall superparamagnetic nanoparticles, fluorine, gadolinium and some types of reporter genes have been used for imaging of stem cells. The core subject of these studies is to investigate the survival and differentiation of stem cells, contrast agent's toxicity and long term following of transplanted cells. The promising results of in vivo and some clinical trial studies may raise hope for clinical stem cells imaging with MRI.