Complete and sustained response after peptide receptor radionuclide therapy in a 66-year-old Filipino male with metastatic pancreatic neuroendocrine tumor: A case report

@#The introduction of peptide receptor radionuclide therapy (PRRT) to the Philippines has allowed for novel approaches in the management of neuroendocrine tumors (NETs). This case report details the management of a 66-year-old Filipino man diagnosed with metastatic pancreatic NET after biopsy and staging with Ga-68 DOTATATE PET-CT. After poor response to somatostatin analogue therapy, the patient was advised to undergo PRRT. Upon completing four cycles of PRRT with Lu-177 DOTATATE, the metastatic hepatic lesions showed resolution and the pancreatic tail tumor exhibited regression, allowing the patient to undergo surgical resection of the primary tumor. On follow-up, he was declared to be in remission with good quality of life and no imaging evidence of recurrence. The case underscores the diagnostic and therapeutic utility of radiolabeled somatostatin analogues along with the importance of a multidisciplinary approach in the management of an initially unresectable metastatic pancreatic NET

The radionuclide imaging and therapy for metastatic prostate cancer / 中华泌尿外科杂志

Metastatic prostate cancer is one of the most malignancies and do harm to the health and life expectancy of men. The popularization and application of 68Gallium or 18Fluorine labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) benefit for the excellent diagnostic efficacy, unique value in the diagnosis of metastatic prostate cancer, clinical decision-making guidance, efficacy in monitoring and prognosis evaluation. 223Radium and 177Lu-PSMA radioligand therapy (RLT) could effectively alleviate bone pain, and prolong the overall survival time (OS) as wellas progression-free survival time (PFS) with good safety. In addition, survival of patients with metastatic prostate cancer is expected to be further improved with the advance in the combination therapies with PSMA RLT, androgen-deprivation therapy (ADT), chemotherapy, targeted therapy and immunotherapy.

Radionuclide therapy for pancreatic neuroendocrine neoplasms / 中国实用外科杂志

Pancreatic neuroendocrine neoplasms(pNENs)are the most common neuroendocrine tumors.For early local pNENs,surgery is the main therapeutic strategy and the tumor can be removed completely.But for those pNENs that cannot be surgically removed or have undergone distant metastasis,peptide receptor radionuclide therapy(PRRT)can be chosen as a first-line therapeutic strategy as pNENs overexpress somatostatin receptors.In recent years,clinical trials and studies on the use of PRRT in pNENs have been increasing rapidly.Many reports have confirmed the efficacy of 90 Y and 177 Lu-labeled somatostatin analogue in pNENs patients.

Emerging management and its impact on radioiodine refractory differentiated thyroid cancer / 中国实用外科杂志

Differentiated thyroid cancer(DTC) generally carries good prognosis through standard treatment. While,it could dedifferentiate into radioiodine refractory differentiated thyroid cancer(RAIR-DTC),which progresses rapidly with high mortality and limited treatment methods. Recently,along with the increasing of studies on genetic features,signal transduction pathways and immune microenvironment of RAIR-DTC,as well as the development of new radionuclide tracers,more theoretical bases have been provided for the targeted therapy of RAIR-DTC.

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.

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.

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.

Peptide Receptor Radionuclide Therapy and the Treatment of Gastroentero-pancreatic Neuroendocrine Tumors: Current Findings and Future Perspectives / 대한핵의학회잡지

PURPOSE AND METHODS: Patients with inoperable andmetastasized neuroendocrine tumors (NETs), particularly those with grades 1 and 2, usually receive treatment with somatostatin analogues (SSAs). Peptide receptor radionuclide therapy (PRRT) has gained momentum over the past two decades in patients who progress on SSAs. 177Lu-DOTATATE is currently the most widely used radiopeptide for PRRT. We reviewed the recent evidence on PRRT and the treatment of gastroentero-pancreatic neuroendocrine tumors (GEP-NETs).RESULTS: ¹⁷⁷Lu-DOTATATE can be used as neoadjuvant treatment in patients with inoperable GEP-NETs, who might be candidate for surgery after treatment and as adjuvant therapy after surgical intervention. Combination treatments of PRRT with chemotherapy or targeted agents as well as combinations of radionuclides in patients with NETs have been explored over the last few years. The majority of patients with NETs experience partial response or have disease stabilization, a small percentage has complete response, while some 30% of patients, however, will have disease progression. The safety and efficacy of retreatment with extra cycles of PRRT as salvage therapy have been evaluated in small retrospective series.CONCLUSION: Overall, there is evidence that disease control and quality of life improve significantly after 117Lu PRRT therapy. Clinical trials on this therapy are scarce, and there is a need for further studies to establish proper management guidelines.

Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors / 대한핵의학회잡지

Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation therapy using a compound of β-emitting radionuclide chelated to a peptide for the treatment of tumor with overexpressed specific cell receptor such as somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical resection should be performed for the curative treatment for NETs when it is feasible; however, a multi-disciplinary approach is needed when locally advanced or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin analogues, as a new treatment modality targeting metastatic or inoperable NETs expressing the SSTR2, have been developed and successfully used for the past two decades. As Lu-177 emits both β- and γ-radiation, it has the ability as a theragnostic agent for NETs compared with only β-emitting yttrium-90 labeled PRRT. Several recent studies reported that Lu-177 gave an overall positive response and improved the patients' quality of life. To fully exploit its potential, large comparative studies are needed for the assessment of distinct efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications and developing new regimens of Lu-177-based PRRT, more dedicated clinical research is required.

Application of peptide receptor radionuclide therapy for gastroenteropancreatic neuroendocrine tumor / 中华消化外科杂志

Peptide receptor radionuclide therapy (PRRT),being investigated as an effective treatment for inoperable gastroenteropancreatic neuroendocrine tumor,has gained much importance in recent years.With increasing data of clinical trials and the exploration of different radionuclides as well as the toxic and side effects,PRRT has developed continuously and play a marked role on the treatment of gastroenteropancreatic neuroendocrine tumor.

The effect of CBL combined with SP in clinical probation teaching of nuclear radionuclide therapy / 中华医学教育探索杂志

Objective To evaluate the effect of case-based learning combined with standardized patients in probation of nuclear radionuclide therapy.Methods 360 interns were randomly assigned separately into CBL+SP group and LBL group (180 people),case based on SP as the center of clinical teaching mode was used for CBL+SP group,while traditional classroom teaching mode was used for LBL group.Theoretical test,case analysis and teaching satisfaction survey were used to evaluate the two teaching mode,using SPSS 20.0 software for statistical analysis of the data.t test was used for two independent samples of both theoretical test and case analysis and chi-square test was used for teaching satisfaction survey.Results The score of theory and case analysis of CBL+SP group was higher than that of LBL group,and the difference had statistical significance [(83.26 ± 4.18) vs.(80.36 ± 3.62),t=-7.041,P=0.000;(85.79 ± 4.15) vs.(81.26 ± 3.96),t=-10.844,P=0.000].Satisfaction survey showed that satisfaction degree of CBL+SP group in stimulating and training the correct clinical thinking,grasping the information skills and cultivating their ability to analyze and solve the problem was higher than that of LBL group,and the difference had statistical significance (x2=40.319,x2=33.620,x2=23.493,x2=23.283;P=0.000).Conclusion Case-based learning combined with standardized patients in probation of nuclear radionuclide therapy can obtain satisfactory teaching effort.

Effect of 89SrCl2 for bone metastasis in Uygur and Han patients with prostate cancer / 肿瘤研究与临床

Objective To analyze contrastly the effect of 89SrCl2 for bone metastasis in Uygur and Han patients with prostate cancer.Methods The curative effects in 75 Uygur and 82 Han patients with prostate cancer bone metastasis were investigated after intravenous injection with 89SrCl2,including palliation of pain.SPECT was used to detect the change of metastasis,level of prostate-specific antigen (PSA) and interleukin-6 (IL-6) were detected by electrochemiluminescence immunoassay.Results After treated with 89SrCl2,the palliation rate,the bone metastases and the level of IL-6 were higher in Uygur patients [82.67 ％ (62/75),75 ％ (56/75),(4.24±1.74) pg/ml] than those in Han patients [60.98 ％ (50/82),52.44 ％ (43/82),(2.81±2.38) pg/ml],and there were statistically significant (P ＜ 0.05).Conclusion 89SrCl2 is more effective for the Uygur patients with prostate cancer bone metastasis than the Han patients,clinical workers should pay more attention to this.

Image-Based Dosimetry of Radionuclide Therapy / 대한갑상선학회지

Radionuclide therapies have been applied in the diverse fields of medicine, and it has been demonstrated the usefulness of it, especially in the field of oncology. Accurate dosimetric assessment is imperative during radionuclide therapy, in order to optimize the treatment efficacy for target sites and to minimize the radiation exposure for normal organ. Recent advancement in imaging technology permits the precise determination of the absorbed dose non-invasively. This imaging based dosimetry can be routinely applicable to the bedside in the near future.

Medical Application of Radiation Internal Dosimetry / 핵의학분자영상

Medical internal radiation dosimetry (MIRD) is an important part of nuclear medicine research field using therapeutic radioisotope. There have been many researches using MIRD for the development of new therapeutic approaches including radiopharmaceutical, clinical protocol, and imaging techniques. Recently, radionuclide therapy has been re-focused as new solution of intractable diseases, through to the advances of previous achievements. In this article, the basic concepts of radiation and internal radiation dosimetry are summarized to help understanding MIRD and its application to clinical application.

The role of electron-emitting radiopharmaceuticals in the palliative treatment of metastatic bone pain and for radiosynovectomy: applications of conversion electron emitter Tin-117m

A variety of radionuclides continue to be investigated and/or clinically used for different therapeutic applications in nuclear medicine. The choice of a particular radionuclide with regard to appropriate emissions, linear energy transfer (LET), and physical half-life, etc., is dictated to a large extent by the character of the disease (e.g., solid tumor or metastatic disease), and by the carrier to selectively transport the radionuclide to the desired site. An impressive body of information has appeared in the recent literature that addresses many of these considerations. This article summarizes and discusses the role of high-LET electron emitters and their advantage in the treatment of cancer or for other disorders in specific situations. Areas such as bone pain palliation, bone malignancy therapy, and radiation synovectomy are covered in greater detail. Projections are made as to the future directions and progress in these areas. A discussion of the various issues related to the selection criteria that are useful for choosing the appropriate radionuclide for a particular application is included. Use of high-LET electron emitters is discussed in greater detail, with particular emphasis on the use of conversion electron emitter tin-117m for various therapeutic applications.

Uma variedade de radionuclídeos continua a ser investigada e/ou clinicamente utilizada para diferentes aplicações terapêuticas em medicina nuclear. A escolha de um radionuclídeo, considerando-se sua emissão apropriada, transferência linear de energia (LET) e meia-vida física é determinada na maior parte pelo caráter da doença (p.ex., tumor sólido ou doença metastática), e pelo carreador que transporta o radionuclídeo seletivamente para o sítio desejado. Um notável conjunto de informações voltadas para essas considerações tem aparecido na literatura recente. Esse trabalho resume e discute o papel de emissores de elétrons de alta-LET e sua vantagem no tratamento do câncer ou para outras doenças em situações específicas. Abordagens relacionadas com o alívio da dor óssea, a terapia da doença óssea e a sinovectomia por radiação são apresentadas detalhadamente. Projeções para o futuro e os progressos nessas áreas são indicadas. Uma profunda discussão relacionada aos critérios de seleção que são úteis para escolher o radionuclídeo apropriado para que uma aplicação particular seja incluída. O uso de emissores de elétrons de alta-LET é discutido em grande detalhe, com particular ênfase no uso do estanho-117m, um emissor de elétron de conversão, para várias aplicações terapêuticas.

Internal Radiation Dosimetry using Nuclear Medicine Imaging in Radionuclide Therapy / 핵의학분자영상

Radionuclide therapy has been an important field in nuclear medicine. In radionuclide therapy, relevant evaluation of internally absorbed dose is essential for the achievement of efficient and sufficient treatment of incurable disease, and can be accomplish by means of accurate measurement of radioactivity in body and its changes with time. Recently, the advances of nuclear medicine imaging and multi?modality imaging processing techniques can provide chance of more accurate and easier measurement of the measures commented above, in cooperation of conventional imaging?based approaches. In this review, basic concept for internal dosimetry using nuclear medicine imaging is summarized with several check points which should be considered in real practice.

Internal Radiation Dosimetry using Nuclear Medicine Imaging in Radionuclide Therapy / 핵의학분자영상

Radionuclide therapy has been an important field in nuclear medicine. In radionuclide therapy, relevant evaluation of internally absorbed dose is essential for the achievement of efficient and sufficient treatment of incurable disease, and can be accomplish by means of accurate measurement of radioactivity in body and its changes with time. Recently, the advances of nuclear medicine imaging and multi?modality imaging processing techniques can provide chance of more accurate and easier measurement of the measures commented above, in cooperation of conventional imaging?based approaches. In this review, basic concept for internal dosimetry using nuclear medicine imaging is summarized with several check points which should be considered in real practice.

Regulatory Problems in Radionuclide Therapy and Suggestions for Systematic Improvement / 핵의학분자영상

Radionuclide therapy has been used for more than 50 years and proved to be a safe and effective modality. However, the patients' right to have the excellent medical service is seriously disturbed by excessive regulations of government institutions such as Korea Institute of Nuclear Safety (KINS), Health Insurance Review Agency (HIRA) and Korea Food and Drug Administration (KFDA). For example, the patients should wait for more than 6 months to have I-131 treatment in many hospitals. It is strongly recommended to mitigate the regulations to resonable levels to solve the problems. If HIRA allow the hospitals to charge reasonable rate for radionuclide therapy room, then more hospitals would invest to build the radionuclide therapy rooms and the patients' waiting time would decrease. The waiting time would also decrease, if KINS allow 2 patients to share a radionuclide therapy room. Finally, it is strongly recommended to lower the threshold for approval of new therapeutic radiopharmaceuticals by KFDA, which would allow new effective therapeutic radiopharmaceuticals to be introduced to clinical practices more easily.

Therapeutic radionuclides / 핵의학분자영상

Since the development of sophisticated molecular carriers such as octereotides for peptide receptor targeting and monoclonal antibodies against various antigens associated with specific tumor types, radionuclide therapy (RNT) employing open sources of therapeutic agents is promising modality for treatment of tumors. Furthermore, the emerging of new therapeutic regimes and new approaches for tumor treatment using radionuclide are anticipated in near future. In targeted radiotherapy using peptides and other receptor based carrier molecules, the use of radionuclide with high specific activity in formulating the radiopharmaceutical is essential in order to deliver sufficient number of radionuclides to the target site without saturating the target. In order to develop effective radiopharmaceuticals for therapeutic applications, it is crucial to carefully consider the choice of appropriate radionuclides as well as the carrier moiety with suitable pharmacokinetic properties that could result in good in vivo localization and desired excretion. Up to date, only a limited number of radionuclides have been applied in radiopharmaceutical development due to the constraints in compliance with their physical half-life, decay characteristics, cost and availability in therapeutic applications. In this review article, we intend to provide with the improved understanding of the factors of importance of appropriate radionuclide for therapy with respect to their physical properties and therapeutic applications.