Nuclear medicine theranostics for the management of differentiated thyroid carcinoma / 西安交通大学学报(医学版)

With the increase of its incidence,differentiated thyroid carcinoma(DTC)has become a global concern.Over the recent decades,the guidelines for the management of DTC have been kept updating along with the development of nuclear medicine theranostics and molecular biology.The present article will systematically expound on the 131I pre-treatment evaluation system based on the clinical practice of nuclear medicine theranostics,the latest evidence-based medical evidence,and guideline recommendations.

Construction and Evaluation of Theranostic Near-infrared Fluorescent Probe for Targeting Inflammatory Brain Edema / 实验动物与比较医学

Objective A novel compound based on near-infrared fluorescence (NIRF) probe was prepared to achieve dynamic monitoring of an inflammatory brain edema model in mice and real-time evaluation of therapeutic effects throughin vivo imaging.Methods The NIRF probe IR-783 was chemically linked with clinical brain edema therapeutic drug furosemide (FSM) to obtain the new compound, IR-783-FSM. The ultraviolet fluorescence properties of the compound were evaluated using an ultraviolet spectrophotometer. The uptake of the compound by mouse macrophage cells RAW 264.7 was detected with in vitro cellular experiments. Its cytotoxicity was evaluated through CCK8 assays. A brain edema model was established in BALB/c mice via intraperitoneal injection of lipopolysaccharide (LPS), confirmed by HE staining and dry-wet weight methods for brain tissues. The mice in the brain edema model were divided into control group, IR-783, and IR-783-FSM treatment groups, receiving intraperitoneal injections of PBS, IR-783, and IR-783-FSM, respectively. Real-time in vivo fluorescence imaging was then performed. The mice in each group were euthanized after 10 hours. Ex vivo brain imaging and dry-wet weight measurements were performed to observe the NIRF imaging characteristics and therapeutic effects of IR-783-FSM on brain edema model.Results The newly synthesized compound, IR-783-FSM, retained the excellent near-infrared fluorescence characteristics of IR-783. It could target mouse macrophages with an IC50 of 48.82 µmol/L. A brain edema model could be successfully constructed with intraperitoneal injection of LPS, with significantly higher brain tissue water content compared to the control group (P<0.01). In vivo imaging showed that IR-783-FSM had a significantly stronger fluorescence signal in the brain edema model than IR-783. Compared to the control group, the brain water content was significantly reduced in the 2, 5, and 8 mmol/L IR-783-FSM treatment groups (P<0.01).Conclusion The newly synthesized NIRF probe IR-783-FSM facilitates dynamic monitoring of brain edema and real-time evaluation of therapeutic effects.

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.

Carbonic anhydrase IX-based tumor imaging and therapy: a review / 生物工程学报

Carbonic anhydrase IX (CAIX) is a transmembrane protein that is specifically overexpressed on the surface of hypoxic tumor cells. With the function of regulating the acidity of tumor cells both inside and outside, CAIX is closely related to tumor proliferation, invasion and metastasis. Therefore, CAIX is a promising target for tumor imaging and therapy. Herein, we summarized recent advances in CAIX-based tumor imaging, therapy and theranostics, and prospected future applications of using CAIX as an anti-tumor target.

Research progress of intelligent reversible drug delivery system / 药学学报

In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

Recent advances in chemical fluorescent probes sensitive to tumor microenvironments / 药学学报

Cancer seriously threatens human life and health, it is urgent for the development of rapid detection, precise localization and effective treatment of tumors. Chemical fluorescent probes that are sensitive to tumor-specific microenvironments have important significance in tumor theranostics and a variety of such probes have been developed. In this review, we classified chemical fluorescent probes that are sensitive to tumor microenvironments according to biological characteristics and microenvironmental changes while combining spectroscopy or response mechanisms, and systematically introduced the research progress of chemical fluorescent probes with sensitivity to hypoxia, low polarity, high viscosity, abnormal pH values and abundant reactive oxygen species in tumor microenvironments, in order to provide references for the development and applications of these probes.

Self-assembled nanoformulations of paclitaxel for enhanced cancer theranostics

Chemotherapy has occupied the critical position in cancer therapy, especially towards the post-operative, advanced, recurrent, and metastatic tumors. Paclitaxel (PTX)-based formulations have been widely used in clinical practice, while the therapeutic effect is far from satisfied due to off-target toxicity and drug resistance. The caseless multi-components make the preparation technology complicated and aggravate the concerns with the excipients-associated toxicity. The self-assembled PTX nanoparticles possess a high drug content and could incorporate various functional molecules for enhancing the therapeutic index. In this work, we summarize the self-assembly strategy for diverse nanodrugs of PTX. Then, the advancement of nanodrugs for tumor therapy, especially emphasis on mono-chemotherapy, combinational therapy, and theranostics, have been outlined. Finally, the challenges and potential improvements have been briefly spotlighted.

Cathepsin B-responsive and gadolinium-labeled branched glycopolymer-PTX conjugate-derived nanotheranostics for cancer treatment

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd

LncRNAs in CONDBITs Perspectives, From Genetics towards Theranostics / Jurnal Sains Kesihatan Malaysia

@#LncRNAs (Long noncoding RNAs) are novel group of ncRNAs and has been discovered to be pervasively transcripted in the genome, characterized as endogenous cellular RNAs consist of more than 200 nucleotides. They are ordered in view of function, transcript length, relation with protein-coding genes and other functional DNA elements, and subcellular localization. Theranostics is a novel study in medicine that combines specific targeted biomolecules based upon molecular-based test. As novel finding in the field of molecular medicine, lncRNA is indispensable tools in theranostics based medicine that allows specific targeting of molecular pathway for diagnostics and therapeutics. LncRNAs may execute as signals, decoys, guides, and scaffolds in their natural capacities. LncRNA expression is controlled by transcriptional and epigenetic factors and processes. LncRNAs also relate detracting biological programs. Here we reviewed lncRNAs in disorders/diseasest horoughly based on CONDBITs perspectives, i.e.: cardiology, oncology, neurology and neuroscience, dermatology, the biology of molecular and bioinformatics, immunology, and technologies (related with “-omics”; transcriptomics and “nano”; nanotechnology). It was narrated the lncRNA biomarkers that abundant in cardiovascular, neurodegenerative, dermatology, and immunology perspective. However, as cancer is the most widely studied disease, more biomarkers are available for this particular case. There are abundant cancer-associated lncRNAs. The most frequent learned lncRNA molecules in cancer are HOTAIR, MALAT1, LincRNA-p21, H19, GAS5, ANRIL, MEG3, XIST, HULC. LncRNAs in cancer diagnosis and monitoring, e.g.: H19 and AA174084 (gastric), HULC (hepatocellular), PCA3 (prostate). Prognostic lncRNAs, e.g.: HOTAIR and NKILA (breast), MEG3 (meningioma), NBAT-1 (neuroblastoma), SCHLAP1 (prostate). LncRNAs predicting therapeutic responsiveness, e.g.: CCAT1 (colorectal), HOTAIR (ovarian). Thus, it is concluded that the CONDBIT perspective is useful to describe the encouraging outlook of this transcriptomics-based medicinal approach.

Advances in the application of iron oxide based magnetic nanoparticles in cancer ther-anostics / 中国肿瘤临床

Cancer theranostics has attracted increasing attention in the area of nanooncology, where the therapeutic drugs and diag-nostic imaging are integrated into a multifunctional nanoplatform. A theranostic nanoparticle can deliver therapeutic drugs and imag-ing agents simultaneously. Iron oxide based magnetic nanoparticles (MNPs) are one of the most typical theranostic nanoparticles and have many excellent properties, such as biosafety, superparamagnetism, and tunable surface modifications and functionalizations. Moreover, they have drug loading capacity along with the distinctive properties of T2 weighted magnetic resonance imaging (T2W MRI), magnetic targeting, and magnetic hyperthermia. Presently, iron oxide based MNPs are being widely used in cancer theranostic research. This paper introduces the general structure of iron oxide based MNPs and reviews their applications in cancer dual/multiple modal imaging (T2W MRI combining T1W MRI, CT, optical imaging, PET/SPECT, and ultrasound) and therapy (chemotherapy, photody-namic therapy, photothermal therapy, and magnetic hyperthermia).

Preparation, in vitro imaging and antitumor activity of the second near-infrared imaging drug-loaded liposomes / 中国药科大学学报

@#The combination of diagnosis and treatment through nanotechnology is conducive to the development of cancer treatment. Fluorescent imaging in the second near-infrared window(NIR-II)developed rapidly in recent years due to its imaging advantages. In this paper, we prepared a novel nano drug system, DOX-IR1061-cationic liposome, in which NIR-II fluorescent probe IR1061 was loaded as imaging agents and doxorubicin was loaded as therapeutic agents. It also explores enhanced cellular uptake and cancer cell inhibition rate through octadecylamine. Our NIR-II performance test on liposomes showed that DOX-IR1061-cationic liposome has NIR-II imaging ability. Analysis of liposome cell uptake behavior and cancer cell inhibition experiments demonstrated that octadecylamine can promote liposome uptake by cells and synergize with DOX to enhance anticancer effects. This suggests that the DOX-IR1061-cationic liposome can be used to achieve imaging and therapy effect with further research value.

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.

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.

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 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.

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 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.

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.

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.

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.