Introduction of nuclear medicine research in Japan.

There were many interesting presentations of unique studies at the Annual Meeting of the Japanese Society of Nuclear Medicine, although there were fewer attendees from Europe than expected. These presentations included research on diseases that are more frequent in Japan and Asia than in Europe, synthesis of original radiopharmaceuticals, and development of imaging devices and methods with novel ideas especially by Japanese manufacturers. In this review, we introduce recent nuclear medicine research conducted in Japan in the five categories of Oncology, Neurology, Cardiology, Radiopharmaceuticals and Technology. It is our hope that this article will encourage the participation of researchers from all over the world, in particular from Europe, in scientific meetings on nuclear medicine held in Japan.

Prognostic value of (18) F-fluoroazomycin arabinoside PET/CT in patients with advanced non-small-cell lung cancer.

This study evaluated the prognostic value of positron emission tomography/computed tomography (PET/CT) using (18) F-fluoroazomycin arabinoside (FAZA) in patients with advanced non-small-cell lung cancer (NSCLC) compared with (18) F-fluorodeoxyglucose (FDG). Thirty-eight patients with advanced NSCLC (stage III, 23 patients; stage IV, 15 patients) underwent FAZA and FDG PET/CT before treatment. The PET parameters (tumor-to-muscle ratio [T/M] at 1 and 2 h for FAZA, maximum standardized uptake value for FDG) in the primary lesion and lymph node (LN) metastasis and clinical parameters were compared concerning their effects on progression-free survival (PFS) and overall survival (OS). In our univariate analysis of all patients, clinical stage and FAZA T/M in LNs at 1 and 2 h were predictive of PFS (P = 0.021, 0.028, and 0.002, respectively). Multivariate analysis also indicated that clinical stage and FAZA T/M in LNs at 1 and 2 h were independent predictors of PFS. Subgroup analysis of chemoradiotherapy-treated stage III patients revealed that only FAZA T/M in LNs at 2 h was predictive of PFS (P = 0.025). The FDG PET/CT parameters were not predictive of PFS. No parameter was a significant predictor of OS. In patients with advanced NSCLC, FAZA uptake in LNs, but not in primary lesions, was predictive of treatment outcome. These results suggest the importance of characterization of LN metastases in advanced NSCLC patients.

Radionuclide Reporter Imaging to Visualize Tumor Hypoxia Ex Vivo and In Vivo.

In vitro studies using cell culture, including three-dimensional cultures without the involvement of tumor vessels, have limitations in simulating complex intratumoral hypoxic conditions in live subjects. To generate experimental hypoxic conditions closer to those observed in humans in clinical settings, in vivo studies are necessary. In addition, visible light generated via bioluminescence and fluorescence is generally unsuitable for in vivo experiments because of low tissue penetration. Furthermore, near-infrared light (NIR), which has the highest tissue penetration among lights of different wavelengths, cannot be assessed precisely in vivo because of the difficulty in correcting tissue absorption and scatter. For in vivo quantitative analyses, imaging modalities that use high tissue-penetrating signals, such as computed tomography (CT) using X-rays, radionuclide imaging using γ-rays, and magnetic resonance imaging (MRI) using electromagnetic waves, are ideal.Therefore, as an advanced protocol for this research purpose, we provide ex vivo and in vivo methods to investigate the genetic response of multiple copies of hypoxia response elements (HREs) to tumor hypoxia in terms of intensity and intratumoral distribution using a human sodium/iodide symporter (hNIS) reporter gene and radionuclide reporter probes (radioiodine and its chemical analog Tc-99m) based on our previous research. This protocol includes cloning an hNIS reporter construct with multiple copies of HREs, establishing stable cell lines of the reporter construct, preparing a mouse subcutaneous xenograft model, and evaluating the genetic response of multiple HREs to tumor hypoxia using digital autoradiography (ARG) ex vivo and using single-photon emission computed tomography (SPECT) or positron emission tomography (PET) in vivo.

A Luciferase Reporter Assay to Detect Cellular Hypoxia In Vitro.

Hypoxia is a hallmark of ischemic cardiovascular diseases and solid malignant tumors. Cellular hypoxia induces numerous physiological and pathological processes, including hematopoiesis, angiogenesis, metabolic changes, cell growth, and apoptosis. Hypoxia-inducible factor-1 (HIF-1) binds to hypoxia response elements (HREs) to selectively induce the expression of various genes in response to hypoxia. Therefore, HREs have been used to develop hypoxia-targeted gene therapy.More than 70 pairs of HREs and hypoxia-inducible genes have been identified. The hypoxia-induced gene expression levels vary among HRE sequences depending on the number of HRE copies and oxygen levels. Most known HREs have not yet been thoroughly studied. Recent studies have revealed that the HRE-mediated effects of hypoxia are cell line-dependent. Herein we describe an in vitro method to investigate gene activation levels and characteristics based on varying the copy number of HREs in response to cellular hypoxia. We explain how to clone HREs into luciferase reporter constructs in the sense, antisense, and dual directions to measure luciferase expression for functional analyses.

Spinal Instability as a Prognostic Factor in Patients With Spinal Metastasis of Castration-resistant Prostate Cancer.

BACKGROUND/AIM: To evaluate the Spinal Instability Neoplastic Score (SINS) for prediction of survival in patients with spinal column metastasis of castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: A retrospective study of spinal instability was performed in patients with CRPC using SINS. Overall survival was evaluated starting from the time of SINS evaluation. The subjects were 42 patients with CRPC among 261 cases diagnosed with metastatic spinal tumors by radiologists, among 42,152 cases that underwent a body computed tomography scan at Kawasaki Medical School Hospital within 32 months from December 2013 to July 2016. RESULTS: The median age was 78 (range=55-91 years), the median prostate-specific antigen (PSA) level at SINS evaluation was 42.1 (0.1-3,121.6) ng/ml, and 11 patients had visceral metastasis. The median periods from diagnosis of bone metastasis and development of CRPC to SINS evaluation were 17 (0-158) and 20 (0-149) months, respectively. The spine was stable in 32 cases (group S) and potentially unstable or unstable in 10 (24%) (group U). The median observation period was 17.5 (0-83) months and 36 patients died. The median survival period after SINS evaluation was longer in group S than that in group U (20 vs. 10 months, p=0.0221). In multivariate analysis, PSA level, visceral metastasis, and spinal instability were significant prognostic factors. The hazard ratio for patients in group U was 2.60 (95%CI=1.07-5.93, p=0.0345). CONCLUSION: Spinal stability evaluated using SINS is a new prognostic factor for survival of patients with spinal metastasis of CRPC.

[Impact of Residual Radioactivity Rate of 99mTc-macro Aggregated Albumin (MAA) in Syringes and Administration Routes with a Focus on Pediatric Nuclear Medicine Examinations].

PURPOSE: The purpose of this study was to evaluate the residual radioactivity in the syringe and route of administration of a low fluid volume 99mTc-macro aggregated albumin (MAA) intended for pediatric nuclear medicine examinations. METHOD: We evaluated the residual characteristics, as the effect of elapsed time from drawing up of radiopharmaceuticals to plastic syringe to administration, and the effect of volume of 99mTcO4- solution to be labeled, the effect of rinsed times of plastic syringe, effect of dose of calculated by consensus guidelines for pediatric nuclear medicine and residual location in injection sets with 99mTc-MAA. Residual radioactivity was measured using planar images obtained by the gamma camera. RESULTS: Residual radioactivity rate of 99mTc-MAA, 99mTc-MAG3, 123I-IMP showed 41.3±1.6%, 14.4±0.6%, 14.6±2.0%, respectively. 99mTc-MAA clearly showed a higher residual rate. Residual radioactivity rate increased with the extension of the elapsed time, and reached a high value of 41.3% in 30 minutes. Residual radioactivity rate was dependent on the different volume of 99mTcO4- to be labeled (4.0 ml and 8.0 ml). Residual radioactivity rate did not change when the number of rinsed was more than one. Residual rate was around 40% at all doses of calculated by consensus guidelines for pediatric nuclear medicine. CONCLUSION: 99mTc-MAA showed the highest residual radioactivity rate among radiopharmaceuticals used in pediatric nuclear medicine examinations. The factor that most affected the residual radioactivity rate of 99mTc-MAA was the elapsed time from draw up to the plastic syringe to administration.

The "Ant-farm"-like Appearance of Restricted Lower Limb Vasculitis on Fluorodeoxyglucose-positron Emission Tomography.

Restricted lower limb vasculitis is a type of localized muscle vasculitis limited to the lower limbs. The usefulness of fluorodeoxyglucose-positron emission tomography (FDG-PET) for the diagnosis of this entity has not yet been reported. We herein report three patients with a fever and persistent lower limb pain. FDG-PET revealed linear and patchy FDG uptakes in their lower limbs. Combined with magnetic resonance imaging and histological findings, they were diagnosed with lower limb vasculitis. Linear and patchy FDG uptakes are considered to reflect the presence of muscle vasculitis. The characteristic "ant-farm"-like FDG-PET images can be a diagnostic clue for the currently overlooked vasculitis.

High incidence of thyroid cancer in focal thyroid incidentaloma detected by 18F-fluorodeoxyglucose [corrected] positron emission tomography in relatively young healthy subjects: results of 3-year follow-up.

As 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is becoming a common imaging modality, the number of thyroid incidentalomas identified by FDG-PET (PET incidentaloma) is increasing. The purpose of this study was to elucidate the risk of cancer in focal thyroid PET incidentaloma in healthy subjects of relatively younger age as well as the usefulness of repeated FDG-PET. The study was conducted with an observation period of three years. A total of 1,501 healthy volunteers (mean age, 43.5+/-9.7 years) underwent the first FDG-PET from August 2003 to July 2004. When focal thyroid PET incidentaloma was found, further diagnostic examination was conducted. When thyroid cancer was suspected, surgical resection was performed with the patient' s agreement. Patients with PET incidentaloma without surgery were offered annual US and FDG-PET and finally FNAB was performed in the fourth year. Focal thyroid PET incidentaloma was observed in 20 subjects. The final diagnoses in 20 subjects were malignant in 11 (ten papillary thyroid carcinoma (PTC) and one thyroid carcinoma showing thymus-like differentiation), indeterminate in one, and benign in eight subjects. Seven patients not treated surgically at the first examination had annual FDG-PET. One patient with PTC showed increasing SUVmax, but another with a benign nodule exhibited a similar increase. Others (one with PTC, one with an indeterminate nodule, and three with benign nodules) exhibited negligible SUVmax changes. When closely examined, focal thyroid PET incidentaloma in relatively young healthy adults has a high probability of malignancy. Repeated FDG-PET to follow up patients with thyroid nodules is ineffective.

Current status of radioligand therapy and positron-emission tomography with prostate-specific membrane antigen.

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein highly expressed by prostate cancer cells. PSMA-based radioligand therapy (RLT) emerged as a promising therapeutic option for prostate cancer in the early 2000s, and has been clinically validated with great enthusiasm during these past two decades. Last year, the European Association of Nuclear Medicine (EANM) published the procedure guidelines for the safe clinical practice of Lutetium-177 (177Lu)-labelled PSMA RLT. In addition, PSMA RLT with alpha-ray-emitting radioisotopes has been also developed recently. Following the clinical use of 177Lu-PSMA RLT, PSMA-targeted positron-emission tomography (PET) with Gallium-68 (68Ga) has been performed inevitably for "theranostics" for the last decade; prostate cancer is going to be treated with PSMA-RLT based on the diagnosis by PSMA-PET. Furthermore, the diagnostic usefulness of 68Ga-PSMA PET has been documented in various diseases beyond prostate cancer more recently. Regrettably, Japan is behind European countries and the United States in this field, and has just made a belated start of their clinical trials. In this review article, we briefly overviewed the current status of PSMA RLT and PSMA PET. We hope that this topic will be a particular focus of attention for most ANM readers in Japan, and that our efforts will help to facilitate the early approval of PSMA RLT and PSMA PET by the Japanese government even if only slightly.

Imaging of Hypoxic Tumor: Correlation between Diffusion-weighted MR Imaging and 18F-fluoroazomycin Arabinoside Positron Emission Tomography in Head and Neck Carcinoma.

We investigated the usefulness of diffusion-weighted imaging (DWI) for detecting changes in the structure of hypoxic cells by evaluating the correlation between 18F-fluoroazomycin arabinoside (FAZA) positron emission tomography activity and DWI parameters in head and neck carcinoma. The diffusion coefficient corresponding to the slow compartment of a two-compartment model had a significant positive correlation with FAZA activity (ρ = 0.58, P = 0.016), whereas the diffusional kurtosis from diffusion kurtosis imaging had a significant negative correlation (ρ = -0.62, P = 0.008), which suggests that those DWI parameters might be useful as indicators for changes in cell structure.

Therapeutic effects of acupuncture in patients with rheumatoid arthritis: a prospective study using (18)F-FDG-PET.

OBJECTIVE: The purpose of this study was to investigate whether improvement of regional inflammatory findings in knee joints of rheumatoid arthritis (RA) could be detected by positron-emission tomography (PET) using (18)F-Fluorodeoxyglucose (FDG) after acupuncture treatments, as well as improvement of systemic inflammatory markers. METHODS: Six RA patients (all female, 61 +/- 12 years old) received 10 acupuncture treatments in 2 months, to 11 traditional acupuncture points around a knee joint considered effective on RA. A visual analogue scale (VAS) for intensity of pain, knee joint range of motion (ROM), face scale for patient mood, and modified health assessment questionnaire (MHAQ) for disability of daily activities were assessed just before and after acupuncture. Maximum standardized uptake value (SUV(max)) and the volume with SUV more than 1.0 [Volume(SUV > 1)] on FDG-PET images as well as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also measured before and after the treatments. RESULTS: VAS, ROM, face scale and MHAQ improved in all patients and significantly after acupuncture, but no significant change was detected in ESR, CRP, SUV(max), or Volume(SUV > 1). CONCLUSIONS: Acupuncture relieves symptom, remedies physical function, and improves quality of life in RA patients, but may have no or very limited anti-inflammatory effect systemically. The regional effects of acupuncture are unlikely to be induced through reduction of regional inflammation. We believe this clinical study is the first step for elucidating therapeutic mechanisms of acupuncture, which must be important for the rational use and further development of acupuncture.

From the respective expert viewpoints of the ANM specialty editors.

Although it may not be well known, the Annals of Nuclear Medicine (ANM) Editorial Committee includes one specialty editor of nuclear medicine physics, one of nuclear medicine technology, one of molecular imaging, and two of radiopharmacology. In addition, a statistics editor and a language editor are also on the committee. Manuscripts submitted to ANM can be peer-reviewed by such specialty editors similar to those submitted to highly ranked journals, which is a great pride and joy to us. To offer our readers a condensed global view on the high-quality research work in the field of nuclear medicine, we have published a mini-review article every year under the joint authorship of the ANM associate editors since 2016. This is our fourth serial review article written by the ANM specialty editors from their respective expert viewpoints.

Effect of drugs containing glucose on FDG-PET image quality.

OBJECTIVE: Patients often take prescription drugs for various diseases or complications that contain several grams of glucose. However, the effect of these glucose-containing medications on the image quality of F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has not been established. This study aimed to evaluate the effect of taking drugs containing glucose before an FDG-PET on the PET image quality. METHODS: In total, 736 continuously enrolled patients who underwent FDG-PET were retrospectively analysed. We investigated the total glucose content in the prescription drugs that each patient took during fasting before the FDG injection, and we divided the patients into three groups according to the amount of glucose in their drugs: group A did not take any drugs containing glucose, group B took sugar-coated tablets (containing trace amounts of glucose), and group C took prescription drugs with glucose an ingredient. Visual scores and quantitative variables with standard uptake value (SUV) for the brain, myocardium, blood, liver, and muscle in the FDG-PET images were analysed and statistically compared across the three groups. RESULTS: In group C, the amount of glucose was 0.63 ± 0.86 g (maximum 4.9 g). For the visual scores, there were no significant differences among the three groups. For the quantitative variables, significant differences were present in the brain SUVmax, muscle SUVmean, brain/blood ratio, brain/liver ratio, and brain/muscle ratio. However, a multivariate analysis showed that the group indicator was not significantly associated with any of the quantitative variables. On the other hand, blood glucose was significantly associated with the visual and quantitative variables. In group C, the correlation coefficient between the amount of glucose and the blood glucose level, the visual scores and the quantitative variables were in the range of - 0.121 to 0.100 and were not significant. CONCLUSIONS: There were no significant differences between glucose-containing medications before FDG-PET and the visual scores and quantitative variables for FDG-PET image. Several grams of glucose in drugs before FDG-PET can be ignored.

Incidence and characteristics of uterine leiomyomas with FDG uptake.

OBJECTIVE: Uterine leiomyomas sometimes show focal 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) images that may result in a false-positive diagnosis for malignant lesions. This study was conducted to investigate the incidence and characteristics of uterine leiomyomas that showed FDG uptake. METHODS: We reviewed FDG-PET and pelvic magnetic resonance (MR) images of 477 pre-menopausal (pre-MP, age 42.1 +/- 7.3 years) and 880 post-MP (age 59.9 +/- 6.8 years) healthy women who underwent these tests as parts of cancer screening. Of 1357, 323 underwent annual cancer screening four times, 97 did three times, 191 did twice, and the rest were screened once. Focal FDG uptake (maximal standardized uptake value > 3.0) in the pelvis was localized and characterized on co-registered PET/MR images. RESULTS: Uterine leiomyomas were found in 164 pre-MP and 338 post-MP women. FDG uptake was observed in 18 leiomyomas of 17 of the 164 (10.4%) pre-MP women and in 4 leiomyomas of 4 of the 338 (1.2%) post-MP women. The incidence was significantly higher in pre-MP women than in post-MP women (chi-square, P < 0.001). Of the 22, 13 showed signal intensity equal to or higher than that of the myometrium on T2-weighted MR images, which suggested abundant cellularity, whereas the majority of leiomyomas without FDG uptake showed low signal intensity. Of the 13 women, 12 examined more than twice showed substantial changes in the level of FDG uptake in leiomyomas each year with FDG uptake disappearing or newly appearing. These changes were observed frequently in relation with menopause or menstrual phases. CONCLUSIONS: Leiomyomas with focal FDG uptake were seen in both pre-and post-MP women with a higher incidence in pre-MP women. Abundant cellularity and hormonal dependency may explain a part of the mechanisms of FDG uptake in leiomyomas. It is important to know that the level of FDG uptake in leiomyomas can change and newly appearing FDG uptake does not necessarily mean malignant transformation.

Assessment of cervical lymph node metastases using FDG-PET in patients with head and neck cancer.

OBJECTIVE: To evaluate the diagnostic accuracy of fluorodeoxyglucose positron emission tomography (FDG-PET) relative to computed tomography (CT) for detecting metastatic cervical lymph nodes in patients with squamous cell carcinoma of the head and neck (HNSCC), and to ascertain the factors that affect this accuracy. METHODS: A total of 1076 lymph nodes obtained from 35 neck dissections in 26 HNSCC patients who preoperatively underwent both FDG-PET and CT were retrospectively analyzed. For pathological metastatic lymph nodes, the lymph node size (short-axis diameter), the ratio of intranodal tumor deposits, and the size of intranodal tumor deposits (maximum diameter of metastatic foci in each lymph node) were histologically recorded. RESULTS: Forty-six lymph nodes from 23 neck sides were pathologically diagnosed metastases. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG-PET evaluated individually per neck side were 74%, 92%, 80%, 94%, and 65%, respectively, whereas those of CT were 78%, 58%, 71%, 78%, and 58%, respectively. FDG-PET detected 100% of metastatic lymph nodes > or =10 mm, intranodal tumor deposits > or =9 mm, and intranodal tumor deposits with a ratio >75%, whereas no nodes or tumor deposits smaller than 5 mm were detected. The spatial resolution limitations of FDG-PET were responsible for 16 of 20 (80%) false-negative PET results in lymph nodes. CONCLUSIONS: FDG-PET is a useful tool for preoperative evaluation of the neck because it accurately detects metastatic lymph nodes > or =10 mm and has fewer false-positive cases than CT. The high specificity of FDG-PET for lymph node metastases may play an important role in avoiding unnecessary neck dissection.

European research trends in nuclear medicine.

Written by associate editors of the Annals of Nuclear Medicine, this invited review article is intended to offer our readers a condensed global view on the high-quality research work that has been published in Europe last year. We have divided this article into five sections. The first three sections from the oncology category include "[18F]fluorodeoxyglucose (FDG) positron-emission tomography (PET) for therapy monitoring in malignant lymphoma", "[18F]fluoromisonidazole (FMISO) PET for hypoxia", and "lymphoscintigraphy update". It is followed by a section on "amyloid PET for Alzheimer's disease" using [11C]Pittsburgh Compound B (PiB) and [18F]florbetapir from the neurology category. The final section reviews three original articles in the field of "basic and translational molecular imaging" regardless of the category, which investigated new PET tracers such as L-4-borono-2-[18F]fluoro-phenylalanine (FBPA), O-(2-[18F]fluoroethyl)-L-tyrosine (FET) and 64Cu-NOTA-pertuzumab in small animals. We hope that this review article will arouse greater interest in our readers in recent European research trends in the field of nuclear medicine.

Decreased myocardial beta-adrenergic receptor density in relation to increased sympathetic tone in patients with nonischemic cardiomyopathy.

UNLABELLED: Cardiac sympathetic function plays an important role in the regulation of left ventricular (LV) function and the pathophysiology of LV dysfunction. (11)C-CGP-12177 ((11)C-CGP) has been used to assess myocardial beta-adrenergic receptor (beta-AR) density in vivo using PET. The aim of this study is to measure myocardial beta-AR density in patients with nonischemic cardiomyopathy and to compare the measurements with various standard parameters of heart failure (HF), particularly with presynaptic function assessed by (123)I- metaiodobenzylguanidine ((123)I-MIBG) imaging. METHODS: (11)C-CGP PET was performed on 16 patients with nonischemic cardiomyopathy and 8 age-matched healthy volunteers using a double injection method. A (11)C-CGP dynamic scan for 75 min was performed after the injection of (11)C-CGP with a high specific activity. After 30 min, (11)C-CGP with a low specific activity was injected. The beta-AR density of the whole LV was calculated on the basis of the graphical analysis method. Additionally, beta-AR density was compared with LV ejection fraction (LVEF), sympathetic presynaptic function assessed using (123)I-MIBG kinetics, and neurohormonal parameters. RESULTS: The beta-AR density of patients was significantly lower than that of healthy volunteers (3.80 +/- 0.96 vs. 7.70 +/- 1.92 pmol/mL; P < 0.0001). In the patients, beta-AR density correlated significantly with LVEF (r = 0.62, P < 0.05). Furthermore, beta-AR density correlated significantly with the (123)I-MIBG washout rate (r = -0.68, P < 0.01) and delayed heart-to-mediastinum ratio (H/M ratio) (r = 0.61, P < 0.05). On the other hand, the correlation between beta-AR density and early H/M ratio was not significant (r = 0.40, P = 0.13). The beta-AR density of patients with severe HF (New York Heart Association functional [NYHA] class III) was significantly lower than that of those with NYHA functional class I or class II HF (3.24 +/- 0.96 vs. 4.24 +/- 0.73 pmol/mL; P < 0.05). CONCLUSION: A reduction in beta-AR density measured by (11)C-CGP PET was observed in patients with nonischemic cardiomyopathy. This downregulation may be due to the increased presynaptic sympathetic tone as assessed by (123)I-MIBG imaging.

Physiological FDG uptake in the ovaries after hysterectomy.

OBJECTIVE: It is known that focal 18F-fluorodeoxyglucose (FDG) uptake is physiologically seen in the ovaries and uterus of premenopausal women in correlation with the menstrual cycle, which may cause false-positive diagnoses on the images of FDG positron emission tomography (PET). The objective of this study was to clarify whether women of reproductive age after hysterectomy whose ovaries were preserved, also showed physiological ovarian FDG uptake. METHODS: We reviewed 26 women after hysterectomy (age 51.1 +/- 5.0 years), who underwent annual cancer screening, including FDG-PET and pelvic magnetic resonance (MR) imaging, three times. RESULTS: Seven women (age 45.9 +/- 5.8 years, range 34-52 years) had at least one ovary, showing changes in its appearance including the size and number of follicles on MR images each year, which suggested that the ovary was functioning. Four of the seven women showed focal FDG uptake (standardized uptake value 4.2 +/- 1.1) that corresponded to the normal ovaries on five PET examinations. Another group of 19 women (age 53.1 +/- 3.1 years, range 47-59 years) who had small ovaries without changes on MR images each year did not show FDG uptake in the ovaries. CONCLUSIONS: Physiological FDG uptake observed in the ovaries of women of reproductive age even after hysterectomy is reasonably common. As it is not easy to determine the hormonal cycle in these women, it is essential to correlate focal FDG uptake in the pelvis with anatomical and morphological findings on MR images to avoid false-positive diagnoses.

[Cardiac receptor imaging].

Molecular imaging has been focused in the field of cardiovascular medicine. With use of suitable radiopharmaceuticals, neuronal function in the cardiovascular system has been assessed in vivo. Of particular, positron emission tomography(PET) plays an important role for in vivo quantification of various neurotransmitter and receptor functions. We have recently developed 11C-labeled CGP12177, hydrophilic beta-adrenoreceptor antagonist, to measure myocardial beta-receptor density(Bmax) in vivo. The basic study showed high uptake in the lung and myocardium which was significantly suppressed by propranolol pretreatment in the rat model, suggesting specific binding of this ligand in the beta-receptors. Bmax was significantly reduced in patients with congestive heart failure. In addition, Bmax was inversely correlated with washout rate of 123I-MIBG from the myocardium in these patients. These new imaging technique has a potential role for assessing severity of heart failure and providing appropriate treatment strategy.

[Myocardial reporter gene expression imaging].

Radionuclide gene expression imaging can visualize and measure transcription activity of target genes noninvasively by co-expressing a reporter gene, of which product can be traced with complementary radioactive reporter probes. While in the cardiac field it was at first aiming at monitoring angiogenic gene therapy, its application is directed to cell tracking in stem/progenitor cell therapy, due to disappointing results in the clinical trials and potential risks of transfer vectors. In this article, we give a general outline of cardiac radionuclide gene expression imaging using reporter genes, including its principle, various combinations of reporter gene/reporter probe, the current status of cardiac gene therapy, and its application for cell tracking.