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.

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.

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.

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.

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.

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.

64Cu-ATSM internal radiotherapy to treat tumors with bevacizumab-induced vascular decrease and hypoxia in human colon carcinoma xenografts.

Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is an antiangiogenic agent clinically used for various cancers. However, repeated use of this agent leads to tumor-decreased vascularity and hypoxia with activation of an HIF-1 signaling pathway, which results in drug delivery deficiency and induction of malignant behaviors in tumors. Here, we developed a novel strategy to treat tumors with bevacizumab-induced vascular decrease and hypoxia using 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM), a potential theranostic agent, which possesses high tissue permeability and can target over-reduced conditions under hypoxia in tumors, with a human colon carcinoma HT-29 tumor-bearing mouse model. The long-term treatment with bevacizumab caused decreased blood vessel density and activation of an HIF-1 signaling pathway; increased uptake of 64Cu-ATSM was also observed despite limited blood vessel density in HT-29 tumors. In vivo high-resolution SPECT/PET/CT imaging confirmed reduced vascularity and increased proportion of 64Cu-ATSM uptake areas within the bevacizumab-treated tumors. 64Cu-ATSM therapy was effective to inhibit tumor growth and prolong survival of the bevacizumab-treated tumor-bearing mice without major adverse effects. In conclusion, 64Cu-ATSM therapy effectively enhanced anti-tumor effects in tumors with bevacizumab-induced vascular decrease and hypoxia. 64Cu-ATSM therapy could represent a novel approach as an add-on to antiangiogenic therapy.

Topics of nuclear medicine research in Europe.

Last year in the European Journal of Nuclear Medicine and Molecular Imaging, we introduced some recent nuclear medicine research conducted in Japan. This was favorably received by European readers in the main. This year we wish to focus on the Annals of Nuclear Medicine on some of the fine nuclear medicine research work executed in Europe recently. In the current review article, we take up five topics: prostate-specific membrane antigen imaging, recent advances in radionuclide therapy, [18F]fluorodeoxyglucose positron-emission tomography (PET) for dementia, quantitative PET assessment of myocardial perfusion, and iodine-124 (124I). Just at the most recent annual meeting of the European Association of Nuclear Medicine 2016, Kyoto was selected as the host city for the 2022 Congress of the World Federation of Nuclear Medicine and Biology. We hope that our continuous efforts to strengthen scientific cooperation between Europe and Japan will bring many European friends and a great success to the Kyoto meeting.

18F-FDG PET/CT Imaging of Epididymal Smooth Muscle Mass Mimicking Recurrent Lymphoma.

An 84-year-old man with a history of diffuse large B-cell lymphoma in remission who had completed chemotherapy 3 years previously was referred for imaging evaluation of disease recurrence. Abnormal accumulation in the left scrotum was demonstrated on F-FDG PET/CT. Subsequent ultrasonography showed a nodular mass lesion in the left epididymis. He then underwent left orchiectomy. Histopathological examination of the mass diagnosed smooth muscle hyperplasia/hamartoma of the left epididymis. Epididymal smooth muscle hyperplasia/hamartoma should be included as a differential diagnosis for malignant scrotal tumor.

Functional evaluation of rat hearts transplanted after preservation in a high-pressure gaseous mixture of carbon monoxide and oxygen.

We recently succeeded in resuscitating an extracted rat heart following 24-48 hours of preservation in a high-pressure gaseous mixture of carbon monoxide (CO) and oxygen (O2). This study aimed to examine the function of rat hearts transplanted after being preserved in the high-pressure CO and O2 gas mixture. The hearts of donor rats were preserved in a chamber filled with CO and O2 under high pressure for 24 h (CO24h) or 48 h at 4 °C. For the positive control (PC) group, hearts immediately extracted from donor rats were used for transplantation. The preserved hearts were transplanted into recipient rats by heterotopic cervical heart transplantation. CO toxicity does not affect the grafts or the recipients. Light microscopy and [(18)F]-fluorodeoxyglucose positron emission tomography revealed that there were no significant differences in the size of the myocardial infarction or apoptosis of myocardial cells in post-transplant hearts between the PC and CO24h groups. Furthermore, at 100 days after the transplantation, the heart rate, weight and histological staining of the post-transplanted hearts did not differ significantly between the PC and CO24h groups. These results indicate that the function of rat hearts is well preserved after 24 hours of high-pressure preservation in a CO and O2 gas mixture. Therefore, high-pressure preservation in a gas mixture can be a useful method for organ preservation.

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.

Report of a nationwide survey on actual administered radioactivities of radiopharmaceuticals for diagnostic reference levels in Japan.

OBJECTIVE: The optimization of medical exposure is one of the major issues regarding radiation protection in the world, and The International Committee of Radiological Protection and the International Atomic Energy Agency recommend establishing diagnostic reference levels (DRLs) as tools for dose optimization. Therefore, the development of DRLs based on the latest survey has been required for nuclear medicine-related societies and organizations. This prompted us to conduct a nationwide survey on the actual administered radioactivity to adults for the purpose of developing DRLs in nuclear medicine. METHODS: A nationwide survey was conducted from November 25, 2014 to January 16, 2015. The questionnaire was sent to all of the 1249 nuclear medicine facilities in Japan, and the responses were collected on a website using an answered form. RESULTS: Responses were obtained from 516 facilities, for a response rate of 41 %. 75th percentile of (99m)Tc-MDP and (99m)Tc-HMDP: bone scintigraphy, (99m)Tc-HM-PAO, (99m)Tc-ECD and (123)I-IMP: cerebral blood flow scintigraphy, (99m)Tc-Tetrofosmin, (99m)Tc-MIBI and (201)Tl-Cl; myocardial perfusion scintigraphy and (18)F-FDG: oncology PET (in-house-produced or delivery) in representative diagnostic nuclear medicine scans were 932, 937, 763, 775, 200, 831, 818, 180, 235 and 252, respectively. More than 90 % of the facilities were within the range of 50 % from the median of these survey results in representative diagnostic nuclear medicine facilities in Japan. Responses of the administered radioactivities recommended by the package insert, texts and guidelines such as 740 MBq ((99m)Tc-MDP and (99m)Tc-HMDP: bone scintigraphy), 740 MBq ((99m)Tc-ECD and (99m)Tc-HM-PAO: cerebral blood flow scintigraphy) and 740 MBq ((99m)Tc-Tetrofosmin and (99m)Tc-MIBI: myocardial perfusion scintigraphy), etc. were numerous. The administered activity of many radiopharmaceuticals of bone scintigraphy ((99m)Tc-MDP and (99m)Tc-HMDP), cerebral blood flow scintigraphy ((99m)Tc-HM-PAO) and myocardial perfusion scintigraphy ((99m)Tc-Tetrofosmin and (99m)Tc-MIBI), etc. were within the range of the EU DRLs and almost none of the administered radioactivity in Japan exceeded the upper limit of SNMMI standard administered radioactivity. CONCLUSIONS: This survey indicated that the administered radioactivity in diagnostic nuclear medicine in Japan had been in the convergence zone and nuclear medicine facilities in Japan show a strong tendency to adhere to the texts and guidelines. Furthermore, the administered radioactivities in Japan were within the range of variation of the EU and the SNMMI administered radioactivities.

Prognostic value of PET/CT with (18)F-fluoroazomycin arabinoside for patients with head and neck squamous cell carcinomas receiving chemoradiotherapy.

OBJECTIVE: The prognostic value of positron emission tomography/computed tomography (PET/CT) with (18)F-fluoroazomycin arabinoside (FAZA) was evaluated in patients with head and neck squamous cell carcinoma (HNSCC) who underwent chemoradiotherapy (CRT). METHODS: Twenty-nine patients with head and neck cancer underwent FAZA PET/CT before treatment. Data acquisition started 2 h after FAZA administration. In 26 patients with squamous cell carcinoma, FAZA uptakes by the primary lesions (tumor-muscle ratio in primary lesion: Pr T/M) and by the lymph node metastases (tumor-muscle ratio in lymph node metastasis) were compared with various clinical parameters. For the HNSCC patients who completed CRT protocol (n = 23), those who experienced disease progression were compared with those who did not experience disease progression with respect to the clinical and PET parameters. The prognostic values of the clinical and PET parameters were then evaluated with regard to progression-free survival (PFS). RESULTS: Pr T/M positively correlated with the lesion's maximum diameter, and it was significantly higher in stage IV lesions compared with stage I-III lesions. No significant differences were observed between the patients who experienced disease progression and those who did not, with respect to the clinical parameters. The average Pr T/M tended to be higher in patients with disease progression, although the differences were not statistically significant (p = 0.086). Kaplan-Meier analysis with log-rank tests indicated that Pr T/M was an only significant predictor of PFS among PET and clinical parameters evaluated (p = 0.010). CONCLUSIONS: FAZA uptake by the primary lesion was a significant prognostic indicator in HNSCC patients undergoing CRT. Hence, FAZA PET/CT may provide useful information in the management of HNSCC patients treated with CRT. Registration number of clinical trial's registry: UMIN000003440.

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.

Performance characteristics of a novel clustered multi-pinhole technology for simultaneous high-resolution SPECT/PET.

OBJECTIVE: Versatile emission computed tomography (VECTor) for small-animal imaging enables fully simultaneous SPECT/PET image acquisition based on clustered multi-pinhole collimation. The present study experimentally evaluated the detailed performance characteristics of the clustered multi-pinhole system for simultaneous (99m)Tc and (18)F imaging from the user perspective. METHODS: Spatial resolution, sensitivity, count rate linearity were determined for the VECTor system (MILabs). Two hot-rod micro-resolution phantoms with 6 sectors were created to test the resolution of (99m)Tc and (18)F. Sensitivity and count rate linearity were measured by scanning (99m)Tc and (18)F point sources positioned at the center of the field of view. Furthermore, we quantified the influence of (18)F on (99m)Tc SPECT images. The ratios of SPECT counts on the (99m)Tc-only and simultaneous (18)F-(99m)Tc at various time points were evaluated as a function of the (18)F-to-(99m)Tc activity concentration ratio. RESULTS: The 0.5-mm hot-rods can be visually distinguished in the (99m)Tc image, and 0.8-mm rods for (18)F remained clearly visible. The point-source sensitivity was 2800 cps/MBq for (99m)Tc and 2899 cps/MBq for (18)F, respectively. Count rates up to 120,000 cps for one bed position were linear for the activity. Spill-over from (18)F into (99m)Tc SPECT images was negligible when the activity concentration of the administered (18)F solution exceeded that of the (99m)Tc solution by up to a factor of 2. CONCLUSIONS: We evaluated the performance characteristics of the VECTor that lead to determination of the optimal administered doses of (99m)Tc and (18)F tracers. We found that the VECTor achieved high resolution and high sensitivity as well as good (99m)Tc and (18)F linearity. Simultaneous SPECT/PET imaging with (99m)Tc and (18)F tracers, and stand-alone (99m)Tc and (18)F imaging using clustered-pinhole collimators is feasible and practical for a wide range of research applications using small animals.

Polymeric Micelle Platform for Multimodal Tomographic Imaging to Detect Scirrhous Gastric Cancer.

Scirrhous gastric cancer (SGC) is a recalcitrant tumor, which is among the most lethal cancers. A critical issue for the improvement of SGC prognosis is the lack of an effective imaging method for accurate detection and diagnosis. Because combined nuclear medicine imaging with magnetic resonance imaging (MRI) has the ability to detect cancer with high sensitivity, and quantitation and spatial resolution, it has potential to overcome the issues with SGC detection. Herein, we designed and synthesized a new block copolymer poly(ethylene glycol)-b-poly(γ-benzyl l-glutamate) linked with a chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-PEG-b-PBLG) to provide a platform for multimodal tomographic imaging. We then successfully prepared DOTA-functionalized polymeric micelles (DOTA/m) measuring 30 nm in diameter, which is an appropriate size to penetrate deeply into tumors with thick fibrosis, including SGC. 111In-labeled DOTA/m highly accumulated in Colon-26 tumors (mouse colon cancer with hyperpermeability), but also in OCUM-2 M LN tumors (SGC with hypopermeability), clearly depicting both tumors by single photon emission computed tomography (SPECT). Gd-labeled DOTA/m clearly visualized OCUM-2 M LN tumors by MRI with high spatial resolution. Moreover, 111In/Gd-labeled micelles, as well as the mixture of 111In- and Gd-labeled DOTA/m demonstrated the capability of this system for selective multimodal SPECT/MR imaging of SCG. Our findings support 111In/Gd-DOTA-labeled micelles as a clinical translationable modality for multimodal tomographic imaging capable of detecting SGC.