Introduction of the targeted alpha therapy (with Radium-223) into clinical practice in Japan: learnings and implementation.


:Radium-223 dichloride (Ra-223) is the first targeted alpha therapy approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with bone metastasis. Ra-223 improved overall survival in the international Phase III ALSYMPCA (ALpharadin in SYMPtomatic Prostate Cancer) study. Ra-223 was also demonstrated to be efficacious and safe in Japanese patients in Phase I and Phase II clinical trials. Ra-223 was approved in Japan for the treatment of patients with CRPC with bone metastasis in 2016. The conduct of clinical studies with radionuclides in Japan involves mandatory compliance with local and international regulations pertaining to radiation protection. Without an existing Japanese framework for the handling of α-emitters in clinical practice, we encountered many challenges to initiate the clinical studies. Therefore, we started on a project to determine best practice on the use of Ra-223 in clinical studies. For this project, we evaluated all applicable laws and regulations on the use of radionuclides in medicine, then examined whether and how the α-emitter Ra-223 could meet these legal and regulatory requirements. This included how to approach the matter of discharging patients administered Ra-223 from hospital and radiation protection for caregivers, general public and medical care professionals. Subsequently, we published Manual on the proper use of radium-223 dichloride injection in clinical trials that summarized the essential requirements necessary to allow the safe use of Ra-223 in clinical trials in Japan. As the result, we succeeded in demonstrating that clinical trials of an α-emitter, Ra-223, could be implemented safely in Japan. Our experience in Japan highlights the importance of a multidisciplinary team-based approach and continued professional training in a clinical setting. This article summarizes the rationale behind the development of this manual. We hope that by sharing our experience and information, we can help other countries considering the introduction of radionuclides for clinical use, and support the future development of radionuclide therapies in a safe and effective manner.


Ann Nucl Med


Hosono M,Ikebuchi H,Nakamura Y,Yanagida S,Kinuya S




Has Abstract


2019-03-01 00:00:00














  • Performance profile of FDG-PET and PET/CT for cancer screening on the basis of a Japanese Nationwide Survey.

    abstract:OBJECTIVE:The aim of this study is to survey the situation of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) cancer screening in Japan and to describe its performance profile. METHODS:"FDG-PET for cancer screening" was defined as FDG-PET or positron emission tomography and computed tomography (PET/CT)...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章,多中心研究


    authors: Minamimoto R,Senda M,Uno K,Jinnouchi S,Iinuma T,Ito K,Okuyama C,Oguchi K,Kawamoto M,Suzuki Y,Tsukamoto E,Terauchi T,Nakashima R,Nishio M,Nishizawa S,Fukuda H,Yoshida T,Inoue T

    更新日期:2007-11-01 00:00:00

  • Usefulness of cerebral blood flow (CBF) measurements to predict the functional outcome for rehabilitation in patients with cerebrovascular disease (CVD).

    abstract:PURPOSE:The objectives of this study were to (1) elucidate the relationship between the mean CBF in the whole brain (Av.mCBF) before rehabilitation of CVD patients and the BI score before and after rehabilitation, (2) determine whether the efficacy of rehabilitation can be predicted by measurement of the Av.mCBF, and (...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Tamamoto F,Sumi Y,Nakanishi A,Okayasu K,Maehara T,Katayama H

    更新日期:2000-02-01 00:00:00

  • Metabolic reserve in normal myocardium assessed by positron emission tomography with C-11 palmitate.

    abstract::Positron emission tomography (PET) with C-11 palmitate has been used in estimating the myocardial utilization of free fatty acid. To assess the metabolic reserve in normal subjects, a PET study was performed at control and during dobutamine infusion at 2 hour intervals in 5 normal subjects. Following monoexponential c...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Tamaki N,Kawamoto M,Takahashi N,Yonekura Y,Magata Y,Nohara R,Kambara H,Kawai C,Konishi J

    更新日期:1991-07-01 00:00:00

  • Unintentional human skeletal imaging with 99mTc-methylene diphosphonate 45 months beyond expiration.

    abstract::Eight patients were inadvertently administered, and imaged with, 99mTc-labeled MDP which was 45 months expired. Two cases are presented. All patients were subsequently imaged with normal MDP. The images obtained with expired MDP were clinically acceptable. No differences in scan abnormalities were observed compared wi...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Riveros EG

    更新日期:1999-10-01 00:00:00

  • The role of adrenocortical scintigraphy in the evaluation of unilateral incidentally discovered adrenal and juxtaadrenal masses.

    abstract::We reviewed the findings of adrenocortical scintigraphy with 131I-6-beta-iodomethyl-19-norcholesterol (NCL-6-131I) of 39 patients to clarify its role in the evaluation of unilateral adrenal or juxtaadrenal masses incidentally discovered by CT, ultrasonography or plain radiography. Twenty-seven benign adrenal masses sh...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Nakajo M,Nakabeppu Y,Yonekura R,Iwashita S,Goto T

    更新日期:1993-08-01 00:00:00

  • Bone metabolic markers as gauges of metastasis to bone: a review.

    abstract::Currently, imaging techniques are the leading methods used to diagnose of metastasis to bone. However, these techniques are expensive, expose patients to toxic and radioactive compounds, and monitor response to treatment poorly; these drawbacks have prompted the search for alternative screening methods. Therefore, bon...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章,评审


    authors: Koizumi M,Ogata E

    更新日期:2002-05-01 00:00:00

  • Visual and semi-quantitative analyses of dual-phase breast-specific gamma imaging with Tc-99m-sestamibi in detecting primary breast cancer.

    abstract:OBJECTIVES:Breast cancer is the most common malignancy for females worldwide. This study was to evaluate the application of dual-phase breast-specific gamma imaging (BSGI) in detecting primary breast cancer. METHODS:Seventy-six patients with indeterminate breast lesions that underwent dual-phase BSGI enrolled in this ...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Tan H,Jiang L,Gu Y,Xiu Y,Han L,Wu P,Zhang H,Shi H

    更新日期:2014-01-01 00:00:00

  • Paradigm shift in theranostics of neuroendocrine tumors: conceptual horizons of nanotechnology in nuclear medicine.

    abstract::We present a comprehensive review of Neuroendocrine Tumors (NET) and the current and developing imaging and therapeutic modalities for NET with emphasis on Nuclear Medicine modalities. Subsequently, nanotechnology and its emerging role in cancer management, especially NET, are discussed. The article is both educative ...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章,评审


    authors: Arora G,Bandopadhyaya G

    更新日期:2018-04-01 00:00:00

  • Tumor thrombus in the inferior vena cava from colon cancer detected by 18F-FDG-PET.

    abstract::We present a case of inferior vena cava (IVC) tumor thrombus detected by fluorine- 18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET). A man underwent operations for the treatment of sigmoid colon cancer at the age of 63. Because tumor markers [carcinoembryonic antigen (CEA) and CA19-9] were increased at...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Kaida H,Ishibashi M,Kurata S,Uchida M,Hayabuchi N

    更新日期:2007-06-01 00:00:00

  • Double-phase (131)I whole body scan and (131)I SPECT-CT images in patients with differentiated thyroid cancer: their effectiveness for accurate identification.

    abstract:OBJECTIVE:This study aims to determine whether a (131)I double-phase whole body scan (WBS) and SPECT-CT images have added value over a single-phase WBS image in identifying benign and malignant lesions in patients with well-differentiated thyroid cancer (DTC) at their first radioactive iodine (RAI) treatment. METHODS:...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Wakabayashi H,Nakajima K,Fukuoka M,Inaki A,Nakamura A,Kayano D,Kinuya S

    更新日期:2011-11-01 00:00:00

  • Aortic knob width reflects left ventricular diastolic function assessed by gated myocardial perfusion single photon emission computed tomography in patients with normal myocardial perfusion.

    abstract:BACKGROUND:Aortic knob width on chest radiography represents the extent of aortic dialation and tortuosity of the aortic arch. We tested the hypothesis that aortic knob width reflected left ventricular (LV) diastolic function assessed by gated myocardial perfusion single photon emission computed tomography (SPECT) in p...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Kurisu S,Higaki T,Sumimoto Y,Ikenaga H,Watanabe N,Ishibashi K,Dohi Y,Fukuda Y,Kihara Y

    更新日期:2017-04-01 00:00:00

  • 99mTc(V)-DMSA and 67Ga-citrate images in a patient with recurrent extraabdominal fibromatosis.

    abstract::67Ga-citrate and 99mTc(V)-DMSA images were obtained in a patient with recurrent extraabdominal fibromatosis of the left calf. The 67Ga-citrate image showed abnormal uptake in the left calf lesion and right calf, which was considered due to probable myositis caused by overexertion. On the other hand, the 99mTc(V)-DMSA ...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Ohta H,Komibuchi T,Tomihara M,Watanabe H,Fujikawa S,Shintaku M

    更新日期:1998-08-01 00:00:00

  • The role of gallium-67 imaging in the detection of foci in recent cases of fever of unknown origin.

    abstract::We have assembled data from patients with fever of unknown origin who underwent gallium scintigraphy during the past 5 years in order to obtain a more current sampling of patients, and evaluated the role of gallium scintigraphy retrospectively. Of the 36 patients studied, gallium scintigraphy was positive and contribu...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Suga K,Nakagi K,Kuramitsu T,Itou K,Tanaka N,Uchisato H,Nakanishi T,Utsumi H,Yamada N

    更新日期:1991-03-01 00:00:00

  • Intratumoral heterogeneity in 18F-FDG PET/CT by textural analysis in breast cancer as a predictive and prognostic subrogate.

    abstract:AIM:To assess the predictive and prognostic value of textural parameters in locally advanced breast cancer (LABC) obtained by 18F-FDG PET/CT. METHODS:Prospective study including 68 patients with LABC, neoadjuvant chemotherapy (NC) indication and a baseline 18F-FDG PET/CT. Breast specimens were grouped into molecular p...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Molina-García D,García-Vicente AM,Pérez-Beteta J,Amo-Salas M,Martínez-González A,Tello-Galán MJ,Soriano-Castrejón Á,Pérez-García VM

    更新日期:2018-07-01 00:00:00

  • In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand: [11C]PK-11195 and animal PET following ethanol injury in rat striatum.

    abstract:OBJECTIVE:To investigate whether [(11)C]PK-11195, a specific peripheral benzodiazepine receptors (PBRs) ligand for positron emission tomography (PET), can show activated microglia in a rat brain injury model. METHODS:On day 1, ethanol was injected into the rat's right striatum (ST) using a stereotaxic operative proced...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Toyama H,Hatano K,Suzuki H,Ichise M,Momosaki S,Kudo G,Ito F,Kato T,Yamaguchi H,Katada K,Sawada M,Ito K

    更新日期:2008-06-01 00:00:00

  • Assessment of ampulla (Takotsubo) cardiomyopathy with coronary angiography, two-dimensional echocardiography and 99mTc-tetrofosmin myocardial single photon emission computed tomography.

    abstract:UNLABELLED:We studied the causative mechanism of ampulla (Takotsubo) cardiomyopathy. METHODS:We examined 7 patients with ampulla cardiomyopathy by means of coronary angiography, two-dimensional echocardiography and 99Tc-tetrofosmin myocardial SPECT at the time of emergency admission (acute phase), at 3 to 5 days after...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Ito K,Sugihara H,Kawasaki T,Yuba T,Doue T,Tanabe T,Adachi Y,Katoh S,Azuma A,Nakagawa M

    更新日期:2001-08-01 00:00:00

  • Quantification of human splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 1).

    abstract::Positron emission tomography (PET) by means of a dynamic state method and H2(15)O was performed to quantify splenic blood flow in 20 patients who had no hepatic functional disorders. Non-linear regression analysis was applied to determine splenic blood flow. In calculating arterial input function for the spleen, our o...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Oguro A,Taniguchi H,Koyama H,Tanaka H,Miyata K,Takeuchi K,Inaba T,Nakahashi H,Takahashi T

    更新日期:1993-11-01 00:00:00

  • Thallium-201 brain SPECT to diagnose aggressiveness of meningiomas.

    abstract::This investigation was conducted to determine the ability of 201Tl brain SPECT with respect to preoperative prediction of lesional aggressiveness of meningioma. Fifty-nine lesions in 42 patients were examined. Early (15 min) and late (3 h) SPECT were obtained. Early uptake ratio (ER; lesion to normal brain average cou...

    journal_title:Annals of nuclear medicine

    pub_type: 临床试验,杂志文章


    authors: Kinuya K,Ohashi M,Itoh S,Sakai S,Yamamoto K,Kakuda K,Nobata K,Terahata S,Taki S,Kinuya S

    更新日期:2003-09-01 00:00:00

  • Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in mantle cell lymphoma.

    abstract:OBJECTIVE:Mantle cell lymphoma (MCL) is an aggressive lymphoma sub-type with poor prognosis and high 18F-FDG avidity at PET/CT; nowadays, no validated criteria for PET/CT in treatment response evaluation and prediction of outcome are present. The aim of study was to investigate whether the metabolic PET/CT features may...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Albano D,Bosio G,Bianchetti N,Pagani C,Re A,Tucci A,Giubbini R,Bertagna F

    更新日期:2019-07-01 00:00:00

  • Evaluation of a direct 4D reconstruction method using generalised linear least squares for estimating nonlinear micro-parametric maps.

    abstract:OBJECTIVE:Estimation of nonlinear micro-parameters is a computationally demanding and fairly challenging process, since it involves the use of rather slow iterative nonlinear fitting algorithms and it often results in very noisy voxel-wise parametric maps. Direct reconstruction algorithms can provide parametric maps wi...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Angelis GI,Matthews JC,Kotasidis FA,Markiewicz PJ,Lionheart WR,Reader AJ

    更新日期:2014-11-01 00:00:00

  • Phase I clinical trial of 99mTc-etarfolatide, an imaging agent for folate receptor in healthy Japanese adults.

    abstract:OBJECTIVE:Technetium etarfolatide ((99m)Tc-EF) is a radioactive diagnostic imaging agent that was developed to assess the expression of folate receptors in tumors. Administering folic acid prior to the administration of (99m)Tc-EF has been shown to improve SPECT images. Here, we conducted a phase I clinical trial to as...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Yamada Y,Nakatani H,Yanaihara H,Omote M

    更新日期:2015-11-01 00:00:00

  • Coincidental visualization of an atypical bronchial carcinoid on Tc-99m-sestamibi scan in Kallmann's syndrome.

    abstract::We report a case of an atypical bronchial carcinoid showing sestamibi uptake. A 27-year-old man with Kallmann's syndrome and hyperparathyroidism had parathyroid scintigraphy with 99mTc-sestamibi. A focal uptake was observed on the right perihilar region, and this right perihilar mass was demonstrated on computed tomog...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Yapar Z,Kibar M,Sükan A,Paydaş S,Zeren H,Inal M

    更新日期:2002-02-01 00:00:00

  • Accelerated BMIPP uptake immediately after reperfused ischemia in the isolated rat heart model.

    abstract:OBJECTIVE:123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) can visualize myocardial fatty acid metabolism and has extensive potential for diagnosing cardiac diseases such as acute coronary syndrome in the clinical setting. Increased BMIPP uptake with decreased perfusion occasionally occurs under acute reperfusion...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Fukushima K,Momose M,Kondo C,Hagiwara N,Sakai S

    更新日期:2011-10-01 00:00:00

  • Usefulness of reinjection image for evaluating viable myocardium in the infarcted zone on exercise thallium-201 SPECT.

    abstract::Reinjection images were obtained in 23 patients with myocardial infarction by the additional injection of 37 MBq of thallium-201 after obtaining 4 hour delayed images on exercise thallium-201 SPECT (TSPECT). A redistribution index (RI) was derived of the changes in perfusion defects between immediate and 4 hour delaye...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Tomiguchi S,Takahashi M,Shimomura O,Kojima A,Hara M,Koga Y,Minoda K,Yasue H,Hayasaki K

    更新日期:1991-11-01 00:00:00

  • Peritoneal tuberculosis with elevated serum CA125 mimicking peritoneal carcinomatosis on F-18 FDG-PET/CT.

    abstract::18F-fluorodeoxyglucose positron emission tomography (F-18 FDG-PET) plays an important role in differentiating benign from malignant tumors. However, some false-positive findings, such as tuberculosis, may occur. We report a case referred for F-18 FDG whole-body PET computed tomography (PET/CT) scan owing to an elevate...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Chen CJ,Yao WJ,Chou CY,Chiu NT,Lee BF,Wu PS

    更新日期:2008-07-01 00:00:00

  • Comparison between single photon emission computed tomography with computed tomography and planar scintigraphy in sentinel node biopsy in breast cancer patients.

    abstract:OBJECTIVE:Radio-guided sentinel node (SN) biopsy is a standard method used in the treatment of early breast cancer. Single photon emission computed tomography with computed tomography (SPECT/CT) has been commonly used for SN detection. SPECT/CT adds precise anatomical information of SN sites, and it is reported that mo...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Koizumi M,Koyama M

    更新日期:2019-03-01 00:00:00

  • PET kinetic analysis: wavelet denoising of dynamic PET data with application to parametric imaging.

    abstract::Physiological functions (e.g., cerebral blood flow, glucose metabolism, and neuroreceptor binding) can be investigated as parameters estimated by kinetic modeling using dynamic positron emission tomography (PET) images. Imaging of these physiological parameters, called parametric imaging, can locate the regional distr...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章,评审


    authors: Shidahara M,Ikoma Y,Kershaw J,Kimura Y,Naganawa M,Watabe H

    更新日期:2007-09-01 00:00:00

  • Associations of physiologic myocardial 18F-FDG uptake with fasting duration, HbA1c, and regular exercise.

    abstract:OBJECTIVE:The variability of physiologic 18F-FDG uptake in the myocardium has hampered the accurate evaluation of cardiac glucose metabolism. We investigated the effects of multiple factors, including fasting duration and physical activity, on the physiologic uptake of 18F-FDG by the myocardium in healthy participants....

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Kang JY,Lee MY,Kim YH

    更新日期:2021-01-02 00:00:00

  • Reducing renal uptake of 111In-DOTATOC: a comparison among various basic amino acids.

    abstract:PURPOSE:Several studies have reported significant renal toxicity after the use of a high dose of 90Y-DOTATOC. Thus, renal protection is necessary in treatments with 90Y-DOTA Tyr3-octreotide (DOTATOC). The infusion of certain positively charged amino acids has been shown to effectively reduce renal uptake of DOTATOC. In...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Lin YC,Hung GU,Luo TY,Tsai SC,Sun SS,Hsia CC,Chen SL,Lin WY

    更新日期:2007-01-01 00:00:00

  • Prediction of response to revascularization in patients with renal artery stenosis by Tc-99m-ethylenedicysteine captopril scintigraphy.

    abstract::The aim of the present study was to assess the predictive value of captopril scintigraphy with the new renal agent 99mTc-ethylenedicysteine (99mTc-EC) for post-interventional improvement in blood pressure. Twelve patients who had persistently high blood pressure with previous demonstration of various degrees of renal ...

    journal_title:Annals of nuclear medicine

    pub_type: 杂志文章


    authors: Uğur O,Serdengeçti M,Karacalioğlu O,Ergün EL,Peksoy I,Cekirge S

    更新日期:1999-04-01 00:00:00