Keiichiro Yoshinaga

Current status of nuclear cardiology in Japan: Ongoing efforts to improve clinical standards and to establish evidence

Nuclear cardiology imaging tests are widely performed in Japan as clinical practice. The Japanese nuclear cardiology community has developed new diagnostic imaging tests using 123I-beta-methyl-p-iodophenyl-pentadecanoic acid, 123I-metaiodobenzylguanidine, and 18F-fluorodeoxyglucose PET for detecting cardiac involvement in sarcoidosis. These tests have become popular worldwide. The Japanese Circulation Society and the Japanese Society of Nuclear Cardiology have published clinical imaging guidelines showing indications and standards for the new imaging tests. JSNC is currently striving to improve the standard of clinical practice and is promoting research activities.

Cardiac sympathetic nervous system imaging with (123)I-meta-iodobenzylguanidine: Perspectives from Japan and Europe

Cardiac sympathetic nervous system dysfunction is closely associated with risk of serious cardiac events in patients with heart failure (HF), including HF progression, pump-failure death, and sudden cardiac death by lethal ventricular arrhythmia. For cardiac sympathetic nervous system imaging, 123I-meta-iodobenzylguanidine (123I-MIBG) was approved by the Japanese Ministry of Health, Labour and Welfare in 1992 and has therefore been widely used since in clinical settings. 123I-MIBG was also later approved by the Food and Drug Administration (FDA) in the United States of America (USA) and it was expected to achieve broad acceptance. In Europe, 123I-MIBG is currently used only for clinical research. This review article is based on a joint symposium of the Japanese Society of Nuclear Cardiology (JSNC) and the American Society of Nuclear Cardiology (ASNC), which was held in the annual meeting of JSNC in July 2016. JSNC members and a member of ASNC discussed the standardization of 123I-MIBG parameters, and clinical aspects of 123I-MIBG with a view to further promoting 123I-MIBG imaging in Asia, the USA, Europe, and the rest of the world.

Focus Issue on Cardiac Sarcoidosis from International Congress of Nuclear Cardiology and Cardiac CT (ICNC 12) Symposium: Improving the Detectability of Cardiac Sarcoidosis—Practical Aspects of 18 F-fluorodeoxyglucose Positron Emission Tomography Imaging for Diagnosis of Cardiac Sarcoidosis—

Cardiac sarcoidosis(CS)increases the risk of cardiovascular event such as conduction abnormalities, ventricular arrhythmia and heart failure in patients with sarcoidosis. Recently the Heart Rhythm Society(HRS)issued a consensus on the detection of CS. In this report, 18 F-fluorodeoxyglucose ( 18 F- FDG)positron emission tomography(PET)is employed in the diagnosis of CS. In 2012, the Japanese Ministry of Health, Labor, and Welfare(JMHLW)approved cardiac 18 F-FDG PET for the detection

Absolute quantification of myocardial blood flow

With the increasing availability of positron emission tomography (PET) myocardial perfusion imaging, the absolute quantification of myocardial blood flow (MBF) has become popular in clinical settings. Quantitative MBF provides an important additional diagnostic or prognostic information over conventional visual assessment. The success of MBF quantification using PET/computed tomography (CT) has increased the demand for this quantitative diagnostic approach to be more accessible. In this regard, MBF quantification approaches have been developed using several other diagnostic imaging modalities including single-photon emission computed tomography, CT, and cardiac magnetic resonance. This review will address the clinical aspects of PET MBF quantification and the new approaches to MBF quantification.

Radiopharmaceutical tracers for cardiac imaging

Cardiovascular disease (CVD) is the leading cause of death and disease burden worldwide. Nuclear myocardial perfusion imaging with either single-photon emission computed tomography or positron emission tomography has been used extensively to perform diagnosis, monitor therapies, and predict cardiovascular events. Several radiopharmaceutical tracers have recently been developed to evaluate CVD by targeting myocardial perfusion, metabolism, innervation, and inflammation. This article reviews old and newer used in nuclear cardiac imaging.

Current Clinical Practice of Nuclear Cardiology in Japan

For the numerous cardiology clinical practices in Japan, nuclear cardiology imaging tests are among the most important diagnostic tools. The Japanese nuclear cardiology community has developed a new application using 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to diagnose cardiac sarcoidosis, as well as new diagnostic imaging tests using 123 I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) and 123 Imetaiodobenzylguanidine (MIBG). These new approaches have become popular worldwide. The Japanese Circulation Society (JCS) and the Japanese Society of Nuclear Cardiology (JSNC) have published clinical imaging guidelines and recommendations showing indications and standards for the new imaging tests. Current nuclear cardiology clinical practices in Japan may provide new insights for nuclear cardiology worldwide.

Feasibility of Quantifying Myocardial Blood Flow with a Shorter Acquisition Time Using 15 O-H 2 O PET

Purpose: The quantification of coronary flow reserve (CFR) calculated as the ratio of the myocardial blood flow (MBF) during adenosine triphosphate (ATP) stress to MBF at rest is a useful method for evaluating the functional severity of coronary artery disease (CAD) using 15 O-H2O positron emission tomography (PET). The shorter acquisition time may reduce dyspnea and other side effects of ATP stress and may also reduce the effect of body movements during data acquisition. However, the impact of the shorter data acquisition time on the accuracy of MBF quantification has not been studied. In this retrospective study, we evaluated the accuracy of the MBF and CFR values obtained with shorter scan times using 15 O-H2O PET. Methods: Thirty patients suspected of having CAD (22 males, 8 females; age 56.5±8.8 yrs) and 17 healthy controls (17 males; age 27.7±6.2 yrs) underwent PET during rest and PET with ATP stress dynamic 15 O-H2O. The MBF was estimated with a one-tissue compartment model analysis. MBF and CFR values were calculated using the first 2-min and 3-min PET data of 15 O-H2O as shorter data acquisitions. These data were compared to the standard 6-min PET acquisition data. Results: With the use of the 3-min data, the regions of interest (ROIs) in the left ventricular (LV) chamber and myocardium could be set for all of the subjects. The intraclass correlation coefficients (ICCs) between the 3-min data and 6-min data of the rest MBF, stress MBF and CFR were 0.869, 0.870, and 0.819 in the patients, and 0.912, 0.910, and 0.930 in the controls. The 3-min CFR data showed a significant difference between the patients and controls (2.22±1.02 vs. 4.02±1.50, p<0.01), as did the 6-min data (2.19±0.92 vs. 4.16±1.39, p<0.01). However, the CFR based on 2-min data did not show a significant difference (1.96±1.66 vs. 2.73±1.03, p=0.088). Using a receiver operating characteristic (ROC) analysis, we observed that both the 3-min and 6-min CFR data could be used to separate the CAD patients and controls. Conclusions: A 3-min, but not 2-min, scan with 15 O-H2O PET can be used for the quantitative evaluation of MBF and CFR.

Multiple Administrations of 64Cu-ATSM as a Novel Therapeutic Option for Glioblastoma: a Translational Study Using Mice with Xenografts

Glioblastoma is the most aggressive malignant brain tumor in humans and is difficult to cure using current treatment options. Hypoxic regions are frequently found in glioblastoma, and increased levels of hypoxia are associated with poor clinical outcomes of glioblastoma patients. Hypoxia plays important roles in the progression and recurrence of glioblastoma because of drug delivery deficiencies and induction of hypoxia-inducible factor-1α in tumor cells, which lead to poor prognosis. We focused on a promising hypoxia-targeted internal radiotherapy agent, 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM), to address the need for additional treatment for glioblastoma. This compound can target the overreduced state under hypoxic conditions within tumors. Clinical positron emission tomography studies using radiolabeled Cu-ATSM have shown that Cu-ATSM accumulates in glioblastoma and its uptake is associated with high hypoxia-inducible factor-1α expression. To evaluate the therapeutic potential of this agent for glioblastoma, we examined the efficacy of 64Cu-ATSM in mice bearing U87MG glioblastoma tumors. Administration of single dosage (18.5, 37, 74, 111, and 148 MBq) and multiple dosages (37 MBq × 4) of 64Cu-ATSM was investigated. Single administration of 64Cu-ATSM in high-dose groups dose-dependently inhibited tumor growth and prolonged survival, with slight and reverse signs of adverse events. Multiple dosages of 64Cu-ATSM remarkably inhibited tumor growth and prolonged survival. By splitting the dose of 64Cu-ATSM, no adverse effects were observed. Our findings indicate that multiple administrations of 64Cu-ATSM have effective antitumor effects in glioblastoma without side effects, indicating its potential for treating this fatal disease.

Time to Move on to the Next Stage and Open our Door to the World

W e have the truly great honor of introducing the new English format of the official journal of the Japanese Society of Nuclear Cardiology(JSNC)under the name Annals of Nuclear Cardiology(ANC). The JSNC Executive Committee has had intense discussions on the promotion of research undertakings and educational activities for members. Immediate past President, Dr. Yoshio Ishida, was eager to improve the quality of the official journal and to include good review articles in it. Under Dr. Ishida7s direction, immediate past Editor-in-Chief, Dr. Kenichi Nakajima, upgraded the JSNC newsletter and it became the journal Shinzo Kaku Igaku (Nuclear Cardiology)in July 2013. Dr. Nakajima established Shinzo Kaku Igaku as a scientific journal and successfully published many significant review articles while also paving the way to publishing original articles in it. In June 2014, Dr. Akira Yamashina took over the role of President and committed to furthering the quality and breadth of basic and clinical research and education for physicians and technologists(1). Dr. Nakajima has since been promoted to Vice-President of JSNC, and I have therefore taken over the important role of Editor-in-Chief. I am grateful to the Executive Board members of JSNC for their confidence in selecting me to serve in this capacity, and, with the collaboration of my new editorial board members, I sincerely hope to set us on the path of excellence. JSNC has had successful annual scientific meetings since 2007. The next step in advancing our work should be to improve our scientific journal and to promote the publication of members7scientific research. In order to present our research to the broader worldwide scientific community, Dr. Yamashina and the Executive Board therefore decided to launch this English version of our scientific journal. I know that many young physicians and technologists have made excellent presentations at several international scientific conferences; however, the number of publications is still limited and some manuscripts have been published in Japanese only. As the Editor-in-Chief, I am responsible for turning our official journal into an international journal.

Improving the worldwide quality of nuclear cardiology practice and research: The role of the official journal

One of the highlights of American Society of Nuclear Cardiology (ASNC) 2015 in Washington DC was intense discussions in the international sessions. Nuclear cardiologists from Europe, South America, the Middle East and Asia, and core ASNC officials attended this session. Speakers from around the world described the current status of nuclear cardiology in their regions and talked about region-specific diseases. The ASNC, through its inclusion of the international session, hopes to become a truly international society. Further, in order to do so, it is important to seek new members from outside of the US. As of July 2016, the total ASNC membership was 3698, a figure that has been stable since 2011. While the number of ASNC members from outside of North America has grown by 25% since 2013 due to a new membership category initiated by ASNC in that year, the total non-North American membership is still quite small, with Americans continuing to make up 89.9% of members. Standards of current clinical practice and research within nuclear cardiology are quite high thanks to the efforts of ASNC. In other parts of the world, however, improvements in terms of the quality of clinical practice and research activities within the field of nuclear cardiology are needed. Through the ASNC 2015 international sessions, we have also recognized the gaps between the US and some regions around the world. Therefore, the mission of ASNC continues to be to expand and to raise the quality of nuclear cardiology around the world.