Teranóstico en medicina nuclear: ¿qué es y qué experiencia tenemos en Colombia? / Teranóstico en medicina nuclear: ¿qué es y qué experiencia tenemos en Colombia?

En la era de la medicina personalizada y de precisión, enfocada en mejorar la atención en salud aprovechando al máximo las oportunidades que ofrecen los desarrollos biomédicos, tecnológicos, sociales y económicos de la actualidad, han aparecido nuevos términos como el de teranóstico. Este término nace de la fusión de los conceptos de terapia y diagnóstico y, aunque fue propuesto en años recientes, hace referencia a un abordaje que se ha utilizado desde hace mucho tiempo (1). El teranóstico consiste en una metodología donde el abordaje diagnóstico se hace enfocado hacia la intervención terapéutica individualizada, buscando proporcionar los mejores desenlaces para el paciente. El área de la medicina nuclear ha sido pionera en el teranóstico, pues el primer tratamiento basado en este concepto se realizó con yodo radiactivo (131I) en pacientes con patología tiroidea. Actualmente, con los avances en imagen molecular e imágenes con genes reporteros (2), cada vez se encuentran disponibles más agentes teranósticos para proporcionar terapias individualizadas o "lesionalizadas", como se han empezado a llamar más recientemente (3). En la presente revisión se expone el abordaje teranóstico en medicina nuclear, enfatizando en el funcionamiento, las aplicaciones más frecuentes y la experiencia que se tiene en Colombia.

In the era of personalized and precision medicine, focused on improving health care by making the most of the opportunities offered by current biomedical, technological, social and economic developments, new terms such as theranostic have appeared. This term was born from the fusion of the concepts of therapy and diagnosis and, although it was proposed in recent years, it refers to an approach that has been used for a long time (1). Theranostic consists of a methodology where the diagnostic approach is focused on individualized therapeutic intervention, seeking to provide the best outcomes for the patient. The area of nuclear medicine has been a pioneer in theranostic, since the first treatment based on this concept was performed with radioactive iodine (131I) in patients with thyroid disease. Currently, with advances in molecular imaging and reporter gene imaging (2), more and more theranostic agents are available to provide individualized or "lesionalized" therapies, as they more recently have come to be called (3). In this review, the theranostic approach in nuclear medicine is exposed, emphasizing how it works, what are the most frequent applications and what experience we have in Colombia

Clinical and pathophysiologic relevance of autoantibodies in rheumatoid arthritis

Abstract Rheumatoid arthritis (RA) is an autoimmune/inflammatory disease affecting 0.5 to 1% of adults worldwide and frequently leads to joint destruction and disability. Early diagnosis and early and effective therapy may prevent joint damage and lead to better long-term results. Therefore, reliable biomarkers and outcome measures are needed. Refinement of the understanding of molecular pathways involved in disease pathogenesis have been achieved by combining knowledge on RA-associated genes, environmental factors and the presence of serological elements. The presence of autoantibodies is a distinctive feature of RA. Rheumatoid Factor and Anti-Citrullinated Protein Antibodies are the two most remarkable autoantibodies in RA and provide different clinical and pathophysiological information. They precede the onset of disease symptoms and predict a more severe disease course, indicating a pathogenetic role in RA. Therefore, they promote a more accurate prognosis and contribute for a better disease management. Several RA-associated autoantibody systems have been identified: Anti-Carbamylated Antibodies, Anti-BRAF, Anti-Acetylated, Anti-PAD4 antibodies and others. Hopefully, the characterization of a comprehensive array of novel autoantibody systems in RA will provide unique pathogenic insights of relevance for the development of diagnostic and prognostic approaches compatible with an effective personalized medicine.

Five-fold Gastrointestinal Electrical Stimulation With Electromyography-based Activity Analysis: Towards Multilocular Theranostic Intestinal Implants

BACKGROUND/AIMS: Motility disorders are common and may affect the entire gastrointestinal (GI) tract but current treatment is limited. Multilocular sensing of GI electrical activity and variable electrical stimulation (ES) is a promising option. The aim of our study is to investigate the effects of adjustable ES on poststimulatory spike activities in 5 GI segments. METHODS: Six acute porcine experiments were performed with direct ES by 4 ES parameter sets (30 seconds, 25 mA, 500 microseconds or 1000 microseconds, 30 Hz or 130 Hz) applied through subserosal electrodes in the stomach, duodenum, ileum, jejunum, and colon. Multi-channel electromyography of baseline and post-stimulatory GI electrical activity were recorded for 3 minutes with hook needle and hook-wire electrodes. Spike activities were algorithmically calculated, visualized in a heat map, and tested for significance by Poisson analysis. RESULTS: Post-stimulatory spike activities were markedly increased in the stomach (7 of 24 test results), duodenum (8 of 24), jejunum (23 of 24), ileum (18 of 24), and colon (5 of 24). ES parameter analysis revealed that 80.0% of the GI parts (all but duodenum) required a pulse width of 1000 microseconds, and 60.0% (all but jejunum and colon) required 130 Hz frequency for maximum spike activity. Five reaction patterns were distinguished, with 30.0% earlier responses (type I), 42.5% later or mixed type responses (type II, III, and X), and 27.5% non-significant responses (type 0). CONCLUSIONS: Multilocular ES with variable ES parameters is feasible and may significantly modulate GI electrical activity. Automated electromyography analysis revealed complex reaction patterns in the 5 examined GI segments.

Theranostics Based on Liposome: Looking Back and Forward / 대한핵의학회잡지

Liposome is one of the oldest yet most successful nanomedicine platforms. Doxil®, PEGylated liposome loaded with doxorubicin (DOX), was approved by the FDA in 1995 for the treatment of AIDS-related Kaposi's sarcoma, and it was the first approval for nanomedicine. Since then, liposome-based therapeutics were approved for the treatment of various diseases and many clinical trials are underway. The success of the liposome-based therapeutics was due to following factors: (1) ease of synthesis, (2) biocompatibility, (3) the ability to load both hydrophilic and hydrophobic agents, and (4) long circulation property after application of polyethylene glycol (PEG). Recently, more functionalities are introduced to liposome platform, which are (1) in vivo imaging probes for optical, magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT), (2) pH and temperature-sensitive lipid moiety, and (3) novel agents for photodynamic and photothermal therapies (PDT, PTT). These conventional and newly tested advantages make the liposome to be one of the most promising nanoplatforms for theranostics.

Perspectives in Radiomics for Personalized Medicine and Theranostics / 대한핵의학회잡지

Radiomics handles imaging biomarker from high-throughput feature extraction through complex pattern recognition that is difficult for human to process. Recent medical paradigms are rapidly changing to personalized medicine, including molecular targeted therapy, immunotherapy, and theranostics, and the importance of biomarkers for these is growing day by day. Even though biopsy continues to gold standard for tumor assessment in personalized medicine, imaging is expected to complement biopsy because it allows whole tumor evaluation, whole body evaluation, and non-invasive and repetitive evaluation. Radiomics is known as a useful method to get imaging biomarkers related to intratumor heterogeneity in molecular targeted therapy as well as one-size-fits-all therapy. It is also expected to be useful in new paradigms such as immunotherapy and somatostatin receptor (SSTR) or prostate-specific membrane antigen (PSMA)-targeted theranostics. Radiomics research should move to multimodality (CT, MR, PET, etc.), multicenter, and prospective studies from current single modality, single institution, and retrospective studies. Image-quality harmonization, intertumor heterogeneity, and integrative analysis of information from different scales are thought to be important keywords in future radiomics research. It is clear that radiomics will play an important role in personalized medicine.

Perspectives for Concepts of Individualized Radionuclide Therapy, Molecular Radiotherapy, and Theranostic Approaches / 대한핵의학회잡지

Radionuclide therapy (RNT) stands on the delivery of radiation to tumors or non-tumor target organs using radiopharmaceuticals that are designed to have specific affinity to targets. RNT is recently called molecular radiotherapy (MRT) by some advocators in order to emphasize its characteristics as radiotherapy and the relevance of dosimetry-guided optimization of treatment. Moreover, RNT requires relevant radiation protection standards because it employs unsealed radionuclides and gives therapeutic radiation doses in humans. On the basis of these radiation protection standards, the development and use of radiopharmaceuticals for combined application through diagnostics and therapeutics lead to theranostic approaches that will enhance the efficacy and safety of treatment by implementing dosimetry-based individualization.

Efforts in the Formation and Development of Nuclear Medicine in Vietnam / 대한핵의학회잡지

The foundations of nuclear medicine in Vietnam were established from 1970. Until now, after 48 years of development, in Vietnam, we have some basic equipment including 31 SPECT, 4 SPECT/CT machines, 11 PET/CT scanners, five cyclotrons, and one nuclear reactor.Many nuclearmedicine techniques in diagnosis and treatment have been routinely performed at provincial and central level health facilities such as tumor scintigraphy, thyroid scintigraphy, bone scintigraphy, kidney scintigraphy, cardiac scintigraphy, and radio-isotope therapy with I-131 and P-32. Selective internal radiation therapy with Y-90 microsphere and I-125 radioactive seed implantation has been also successfully applied in some big hospitals. However, there are still many difficulties for Vietnam as the lack of new widely used radioisotopes such as Ga-67, Cu-64, Samarium-153, and Lutetium-177 and the lack of nuclear medicine specialists. In the future, we are putting our efforts on the applications of new isotopes in diagnosis and treatment of cancers (theranostic) like Ga-68-DOTATATE, Lutetium-177-DOTATATE, Ga-68-PSMA, and Lutetium-177-PSMA, equipping modern nuclear medicine diagnostic tools, strengthening the human resources training in nuclear medicine. At the same time, we are trying our best to strengthen the cooperation with international nuclear medicine societies in over the world.

Nuclear Theranostics in Taiwan / 대한핵의학회잡지

Boron neutron capture therapy and Y-90 radioembolization are emerging therapeutic methods for uncontrolled brain cancers and hepatic cancers, respectively. These advanced radiation therapies are heavily relied on theranostic nuclear medicine imaging before the therapy for the eligibility of patients and the prescribed-dose simulation, as well as the post-therapy scanning for assessing the treatment efficacy. In Taiwan, the Taipei Veterans General Hospital is the only institute performing the BNCT and also the leading institute performing Y-90 radioembolization. In this article, we present our single institute experiences and associated theranostic nuclear medicine approaches for these therapies.

Theranostics in India: a Particularly Exquisite Concept or an Experimental Tool / 대한핵의학회잡지

The term theranostics is a combination of a diagnostic tool that helps to define a right therapeutic tool for specific disease and paves the approach towards personalized or precision medicine. In Nuclear Medicine, a diagnostic radionuclide is labeled with the target and once expression is documented, the same target is labeled with a therapeutic radionuclide and treatment is executed. The theranostic concept was applied first time in 1964 in the treatment of thyroid cancer with I-131 (RAI). Over the years, other theranostic radiotracers became available indigenously from the Bhabha Atomic Research Centre (BARC) in the country. Currently Lu-177 is produced in India and peptides like DOTATATE and PSMA are available in a kit form indigenously. At the present time, the radionuclide therapies of oncological disorders which are being performed in India are mainly for neuroendocrine tumors (NET) and metastatic castration resistant prostate cancer (mCRPC). The main constraints pertaining to this concept is the cost of treatment and awareness among the clinicians which are gradually being taken care of by the private health insurance and our participation in disease management group meetings respectively. The theranostic concept has become popular over the years and has the potential for sustained growth.

Current Status and Growth of Nuclear Theranostics in Singapore / 대한핵의학회잡지

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.

Theranostics in Bangladesh: Current Status, Challenges, and Future Perspective / 대한핵의학회잡지

BACKGROUND AND CURRENT STATUS OF THERANOSTICS: Therapeutic nuclear medicine (NM) in Bangladesh began in the early 1980s with the application of radioactive iodine for treatment of thyroid cancer and primary hyperthyroidism. Since then, NM practice has remarkably developed in the country with the advancement of instrumentation, radiopharmacy, and information technology. The government took the initiative to establish four PET-CTcenters at different NMcenters, including one at the National Institute of Nuclear Medicine and Allied Sciences (NINMAS). A further development is the installation of a cyclotron center (18-MeV cyclotron) at NINMAS by the government's fund. Currently, NM is providing good health services to oncology patients throughout the country. More than 20 NM centers are functioning in different parts of the country, and therapeutic NM has an important place. However, conventional radioactive iodine still remains the major theranostic application.CHALLENGES AND FUTURE PERSPECTIVE: The expansion and development of therapeutic NM for other cancers have been limited due to a number of challenging factors. A brief overview of the history and current status ofNMin Bangladesh is presented here with an examination of factors that pose as obstacles to the introduction and development of new therapeutic technologies. Finally, future perspectives are discussed with ways to mitigate existing problems and challenges.

Perspective in Nuclear Theranostics Using Exosome for the Brain / 대한핵의학회잡지

Owing to its highly biocompatible property as naturally produced nanoscale particle and drug carrying ability, exosome has attracted much interest in the biomedical area. Versatile functions of exosome in biological system play an important role in elucidating mysterious and unknown biological processes and pathological disease progression. For usage of exosome as brain disease therapeutics, even though the ability of exosomes crossing blood brain barrier (BBB) is not well clearly proven, the small size and their own characteristics possessing cell-derived molecular contents may provide great and beneficial tools for brain delivery and brain-associated disease therapy. A variety of trials related to bioapplications using stem cell-derived exosome in regenerative therapy or autologous exosome shuttling inhibitor targeting brain disease-associated protein marker enhance possibility of exosome toward clinical application. The radionuclide PETor SPECT imaging of radiolabeled exosome will be clearly able to provide accurate clues for analyzing their whole body distribution, targeting efficacy, and the degree of non-specific tissue uptake. In this perspective, the practical information on thranostics of exosome for brain delivery and therapy is offered and radionuclide-based exosome applicability will be dealt with.

Nuclear Theranostics in Asia: In vivo Companion Diagnostics / 대한핵의학회잡지

No abstract available.

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.

Nuclear Theranostics in Turkey / 대한핵의학회잡지

Nuclear theranostics functions as a bridge which connects targeted diagnosis to targeted therapy, just like Turkey functions as a geographical bridge which connects Asia to Europe. This unique geographical site of the country plays an important role with regard to introduction of novel scientific and technologic improvements, which originate from one continent to another, in the era of accelerated information. The first nuclear medicine practice in Turkey started in the beginning of 1950s with the first radioiodine treatment, which actually was a debut for nuclear theranostics in Turkey, years before many other countries in the world. For the time being, along with radioiodine treatment, many other theranostic applications such as I-131 MIBG treatment, Lu-177/Y-90 DOTA peptide treatment, Lu-177 PSMA treatment, Y-90 microsphere treatment, and bone palliative treatment are being performed in many centers countrywide. As science and technology improves, novel theranostic applications are eagerly awaited to be introduced in near future. This paper summarizes the story of nuclear theranostics in Turkey and aims to give an overview on the current status of theranostic applications in Turkey.

The Emergence of Theranostics in the Philippines: Overcoming Challenges and Bringing Hope / 대한핵의학회잡지

Medical managements are becoming personalized while diseases are being understood at the molecular level. Nuclear medicine is one of the fields actively contributing to this development. In particular, theranostics, a combinatorial term for therapy and diagnostics, enables accurate imaging and subsequent targeted radionuclide treatment. Due to its high impact in healthcare, many countries have begun to offer Ga-68 PET/CTscans and Lu-177 therapies. The Philippines has followed suit through the initiative of this author and able support of the administration and staff of St. Luke's Medical Center. The Ga-68 DOTATATE and PSMA PET/CT scans became officially available in January 2018 while the first peptide receptor radionuclide therapy for neuroendocrine tumor and first PSMA radioligand therapy for prostate cancer occurred in May and June 2018, respectively. Amidst past, present, and future challenges, theranostics has emerged in the Philippines, offering hope to cancer patients in the country.

Nuclear Theranostics in Indonesia: Past, Present, and Future / 대한핵의학회잡지

Nuclear medicine in Indonesia has a quite long history since the late 1960s. There are some problems and obstacles that have to be solved and overcome in order to develop nuclear medicine services, spread the services to reach every target area, and implement new novel therapeutic nuclear medicine as well. The right strategy and strong effort should be performed for a successful result. Theranostics nuclear medicine will play a more prominent role in the management of cancer patients.

Activities for the Development of Targeted Radionuclide Therapy in Japan / 대한핵의학회잡지

Targeted radionuclide therapy (TRT) is unique because of its efficacy and its theranostic feature in the era of precision medicine. So far, introduction of new TRT has not been going well in Japan due to several reasons including strict regulations, shortage of facilities for TRT, and insufficient reimbursement for TRT in clinic. Japanese community had several strategies to develop TRT in these 10 years, including the establishment of the National Conference for Nuclear Medicine Theranostics in which physicians, scientists, patients, people supporting patients, and industrial people gather. To promote TRTwith supports from the government, the preparatory committee for the establishment of Japan Foundation of Medical Isotope Development (JAFMID) was launched. I would like to call TRT “Precision Nuclear Medicine.” When we can add genomic information here, we can put it to new stage of cancer therapy. It is time for us.

Nuclear Medicine Theranostics: Perspective from Pakistan / 대한핵의학회잡지

Nuclear medicine has been offering diagnostic and therapeutic solution since the introduction of radioactive iodine for thyroid diseases since decades. However, the concept of theranostics has given a new found impetus to the use of pairs of radiopharmaceuticals for diagnosis and treatment. Presented here is a perspective on theranostics from Pakistan.

Dawn of Theranostics in Myanmar (Dream, Reality, and Constraint) / 대한핵의학회잡지

Prostate cancer is third common malignancy in men of old age (average 65 years) in Myanmar. Currently, serum PSA and bone scan are the markers of choice. Because of the evidence-based, promising success of ⁶⁸Ga-PSMA PET-CT and 177Lu-PSMA theranostics in prostate cancer worldwide, (99m)Tc-PSMA SPECT-CT imaging and ¹⁷⁷Lu-PSMA therapy has launched as a stepping-stone of theranostics in Myanmar with the available facilities. Twelve cases of prostate cancer patients were imaged with 600 MBq of (99m)Tc-PSMA I+S SPECT-CT. Four metastatic castration resistant prostate cancer (MCRPC) patients with abnormal result were treated with ¹⁷⁷Lu-PSMA. The protocol consists of 6–8 GBq of ¹⁷⁷Lu-PSMA, three successive doses at interval of 4–6 weeks. Post-therapy SPECT-CT imaging was done. All treated patients were improved by free of bone pain, and fall/rise in serum PSA level. Two patients with extensive skeletal metastases succumbed to complications. The results are well documented and present at the multidisciplinary conferences for clinical awareness. Theranostics in prostate cancer with available facilities is an additional boon to our health care professionals to upgrade cancer management in Myanmar. This paper provides the technology with cost effectiveness and benefit to prostate cancer patients of Myanmar.