Search

123I thyroid scintigraphy can be performed with either a low energy or medium energy collimator. The high-energy photon emissions from 123I cause septal penetration with scattered photons, which deteriorate image quality. The aim of this study is to evaluate the impact of collimator choice on 123I thyroid scintigraphy in clinical practice. Methods: Forty seven patients who received thyroid planar scintigraphy with both a low energy high resolution (LEHR) collimator and a medium energy (ME) collimator were prospectively recruited using the same imaging protocol. Image quality, collimator sensitivity, and estimation of thyroid size were assessed between LEHR and ME collimators, and were compared with thyroid ultrasonography as the gold standard. Results: Images acquired with the ME collimator demonstrate less scattered background noise, improved thyroid to background contrast, and increased sensitivity in the thyroid gland compared to images acquired by the LEHR collimator. Manual measurement of the thyroid length is more accurate by using the ME collimator. Automatic estimation of the thyroid area size by using the same thyroid cutoff threshold is larger in ME collimator images than in LEHR collimator images. Conclusion:123I thyroid scintigraphy using the ME collimator generates cleaner images with less background noise and has higher collimator sensitivity for thyroid imaging compared to the LEHR collimator. Different thyroid cutoff threshold should be used to estimate the thyroid area size and volume between low and medium energy collimators.

In contemplating peer-reviewed information and the business of science divulgation, in which we all are immersed, one may wonder what legacy a very quoted article will hand down to posterity and what core of knowledge will stand the tests of time, of fashion, and of planned obsolescence of

Radioiodines have a long history in nuclear medicine. Herein, we discuss the production, properties and applications of these versatile iodine-based imaging and theragnostic agents. There are 38 isotopes of iodine (I) including one stable form (127 I). The most common radionuclides used in medical imaging and treatment, including Iodine-123 (123 I), Iodine-124 (124 I), Iodine-125 (125 I) and Iodine-131 (131 I), are discussed in this review.

Sympathetic innervation of the heart plays an important role in the pathophysiology of diseases, especially congestive heart failure and arrhythmias. Iodine-123 metaiodobenzylguanidine (I-123 MIBG) scintigraphy allows for early detection of problems by imaging at the neurotransmitter level before cardiac structural changes occur. In this way, it is possible to correctly manage the diagnosis and treatment processes of the patients. The main purpose of this guide is to ensure the national standardization of cardiac I-123 MIBG scintigraphy applications. In addition, it is intended to guide nuclear medicine doctors in the proper execution of indications, imaging and clinical processes, evaluation and reporting stages.

Small actinium-225-labeled prostate-specific membrane antigen (PSMA)-targeted radioconjugates have been described for targeted alpha therapy of metastatic castration-resistant prostate cancer. Transient binding to serum albumin as a highly abundant, inherent transport protein represents a commonly applied strategy to modulate the tissue distribution profile of such low-molecular-weight radiotherapeutics and to enhance radioactivity uptake into tumor lesions with the ultimate objective of improved therapeutic outcome. Two ligands mcp-M-alb-PSMA and mcp-D-alb-PSMA were synthesized by combining a macropa-derived chelator with either one or two lysine-ureido-glutamate-based PSMA- and 4-(p-iodophenyl)butyrate albumin-binding entities using multistep peptide-coupling chemistry. Both compounds were labeled with [225Ac]Ac3+ under mild conditions and their reversible binding to serum albumin was analyzed by an ultrafiltration assay as well as microscale thermophoresis measurements. Saturation binding studies and clonogenic survival assays using PSMA-expressing LNCaP cells were performed to evaluate PSMA-mediated cell binding and to assess the cytotoxic potency of the novel radioconjugates [225Ac]Ac-mcp-M-alb-PSMA and [225Ac]Ac-mcp-D-alb-PSMA, respectively. Biodistributions of both 225Ac-radioconjugates were investigated using LNCaP tumor-bearing SCID mice.

Goiter with an intrathoracic component is relatively common; however, it is less common to see extent outside the anterior or posterior mediastinum. We present a case of intrathoracic goiter of significant size and abnormal placement which is examined using both 99mTc-pertechnetate and iodine-123 single-photon emission computed tomography/computed tomography.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Russian Science Foundation BACKGROUND To date, radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) is a valuable treatment option. So far there are no clear predictors of the effectiveness of AF ablation. Nowadays, the association of cardiac sympathetic nervous system and the development and maintenance of AF has been showed. The association between сardiac sympathetic system impairment, assessed by 123I-MIBG scintigraphy and RFCA effectiveness was shown previously. However, the is lack of data concerning to prognostic value of MIBG scintigraphy in patients with different forms of AF – persistent (PAF) and long-standing persistent (LSPAF). PURPOSE To study the prognostic significance of 123I-MIBG scintigraphy in RFCA efficacy in patients with persistent and long-standing persistent AF. METHODS The study enrolled 36 patients with drug-resistant AF (both persistent (n = 20) and long-standing persistent (n = 16) forms). All patients had comorbidity as chronic coronary syndrome and hypertension. A comparison group (n = 10) was also enrolled in the study. It includes patients with chronic coronary syndrome and arterial hypertension (without arrhythmia). All patients underwent 123I-MIBG and 99mTc-MIBI scintigraphy to evaluate the cardiac sympathetic activity and myocardial perfusion, respectively. Patients with AF performed RFCA. After of 1 year follow-up patients were examined for AF recurrence. The AF recurrence was considered to be an AF of at least 30 sec duration on a 12-lead ECG or on the Holter monitoring. RESULTS During the follow-up period, AF recurrences were reported in 7 (35%) PAF patients and in 8 (50%) LSPAF patients. According to multivariate analysis only a high pre-ablation washout rate of 123I-MIBG (WR) in PAF patients (OR: 1.668; 95% CI: 1.093–2.548) and large pre-ablation 123I-MIBG/99mTc-MIBI mismatch score in LSPAF patients (OR: 2.155; 95% CI: 1.192–3.897) were independent predictors of AF recurrence after RFCA. ROC analysis indicated that in PAF patients with higher WR ≥ 20.8% (AUC: 0.968; Sensitivity: 100 %; Specificity: 45%; p < 0.05) and LSPAF patients with larger 123I-MIBG/99mTc-MIBI mismatch score ≥ 12.5 % (AUC: 0.942; Sensitivity: 81 %; Specificity: 28 %; p < 0.05) had a higher risk of AF recurrence after RFCA. CONCLUSION In AF patients the incidence of arrhythmia recurrence after RFCA is associated with impaired cardiac sympathetic nervous activity. In PAF patients the values of 123I-MIBG washout rate can predict AF recurrence. In LSPAF patients innervation/perfusion mismatch has prognostic value in terms of AF recurrence.

Radiopharmaceuticals have been developed to image selectively most of the organ systems of the body. Most commonly, these agents are labelled with the gamma-emitters technetium-99m, iodine-123 or indium-111. The most widely used studies are skeletal scintigraphy, myocardial perfusion imaging, and lung ventilation and perfusion imaging; the targeting agents used are, respectively, bisphosphonate compounds that bind to the hydroxyapatite matrix, lipophilic cations that are trapped in the mitochondria of myocytes, aerosols that outline the airways and particles that are trapped in pulmonary capillaries. If targeting is sufficiently high, the same or similar agents can be labelled with beta- or alpha-particle-emitting radionuclides for therapy. The most common radionuclide therapy is iodine-131 sodium iodide for benign or malignant thyroid disease. After many years of promise, there has been a great expansion in the use of radionuclide therapy with the recent introduction of lutetium-177 somatostatin-receptor-binding peptides (e.g. DOTATATE) for the treatment of neuroendocrine tumours and radium-223 chloride for use in metastatic prostate cancer.

International audience; Introduction: This study aims to reveal the feasibility and potential of molecular connectivity based on neurotransmission in comparison with the metabolic connectivity with an application to dopaminergic pathways. For this purpose, we propose to compare the neurotransmission connectivity findings using 123I-FP-CIT SPECT and 18F-FDOPA PET with the metabolic connectivity findings using 18F-FDG PET.Methods: 18F-FDG PET and 123I-FP-CIT SPECT images from 47 subjects and 18F-FDOPA PET images from 177 subjects, who had no neurological or psychiatric disorders, were studied. Interregional correlation analyses were performed at the group level to determine the midbrain's connectivity via glucose metabolic rate using 18F-FDG PET and via dopaminergic binding potential using 123I-FP-CIT SPECT and 18F-FDOPA PET. SPM-T maps of each radiotracer were generated, and masks used to highlight the significant differences obtained among the imaging modalities and targets.Results: The three dopaminergic pathways (i.e., nigrostriatal, mesolimbic, and mesocortical) were identified by 18F-FDG PET (1599 voxels, with a Tmax value of 12.6), 123I-FP-CIT SPECT (1120 voxels, with Tmax value of 5.1), and 18F-FDOPA PET (6054 voxels, with Tmax value of 11.7) for a T voxel threshold of 5.10, 2.80, and 5.10, respectively. Using the same T voxel threshold of 5.10, 18F-FDOPA PET showed more specific findings than 18F-FDG PET with less voxels identified outside these pathways (- 9323 voxels), whereas no significant voxels were obtained with 123I-FP-CIT SPECT at this threshold.Conclusion: The present study illustrates the feasibility and interest in using molecular connectivity with 18F-FDOPA PET for dopaminergic pathways. Such analyses could be applied to specific diseases involving the dopaminergic system.

ICD in primary prevention reduced mortality in patients with heart failure (HF); however, in about 80% of the ICD recipients an event requiring a device intervention will never occur. Thus, a reliable screening test included in a multiparametric approach to appropriately select patients to ICD implantation is increasingly required. Aim of the work was to assess if the Iodine-123 Meta-Iodobenzylguanidine scintigraphy (123I-mIBG) could be useful to identify patients with HF who would not benefit from the ICD implantation because at low risk of arrhythmias. This is a retrospective multicentre study on patients undergoing 123I-mIBG from February 2012 to December 2015. Inclusion criteria where: age ≥ 18 years old, LVEF ≤ 35% with idiopathic or ischemic heart disease, no previous malignant ventricular arrhythmias. Patients were divided in two groups based on of late H/M < or ≥ 1.60 on 123I-mIBG. Primary end-point was occurrence of malignant arrhythmias. Secondary end-point was occurrence of cardiac death and hospitalization for worsening HF. MACE were mortality and malignant arrhythmias. Eighty-one patients were enrolled (mean age: 69 years). On 123I-mIBG, 54 patients had late H/M

Search and synthesis of glucose derivatives for nuclear medicine is of great current interest. Being a promising analogue of glucose, D-glucosamine iodine labeled glucose derivatives can be applied in rheumatoid arthritis radionuclide diagnostics and therapy as a radiopharmaceutical. The purpose of the study. Synthesis of a new iodine labeled D-glucosamine derivative; development of the iodine-123 labeling method and the obtained glucose derivative biostudy. Materials and methods. Synthesis of 2-N-(6-iodohexanoyl)-D-glucosamine was carried out through established techniques in organic chemistry. Infrared spectroscopy and nuclear magnetic resonance spectroscopy were used to establish the test compound structure. Isotope change between iodine-127 and iodine-123 of glucosamine derivative was conducted using the heating of mix of the compound and Na123I in acetone. The radio-TLC method was applied to estimate the radiochemical purity of 2-N- (6-iod-123-hexanoyl) -D-glucosamine. The safe application and test of drug pharmacokinetic parameters study was performed on intact Wistar male rats. Results. An original 2-N-(6-iodohexanoyl)-D-glucosamine synthesis method was proposed. According to the method, an intermediate synthesis succimide-1-yl 6-iodohexanoate was obtained by the cyclohexanone oxidative cleavage reaction. The radiochemical purity of 2-N-(6-iodo-123-hexanoyl)-D-glucosamine was more than 97%. Conclusion. 2-N-(6-iodohexanoyl)-D-glucosamine was synthesized and iodine-123 labeled. When investigating the proposed radiopharmaceutical safety and pharmacokinetics, it was shown the drug lacks acute toxicity through intravenous injection and is excreted renally by glomerular filtration.

A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts derived from a planar acquisition approximately 4 hours after injection of 123I-mIBG, is a strong predictor of outcomes in patients with stable class II-III heart failure and LVEF ≤ 35%. This study assessed the test–retest reproducibility of the H/M ratio in such patients. 47 subjects with class II-III systolic heart failure and LVEF ≤ 35% were tested at two time intervals separated by 5 to 14 days. Subjects were imaged twice on the same camera using the same radionuclide dose. Images were sent to a core analysis lab, where three nuclear technologists independently determined the H/M ratios. The primary endpoint was test–retest H/M ratio reproducibility calculated as the absolute difference in mean value determined by the three readers. Mean subject age was 65 ± 12 years, 85% were male, and mean BMI was 29 ± 6 kg/m2. Mean injected activity was 10.18 ± 0.43 mCi for first dose and 10.09 ± 0.52 mCi for the second dose. The mean and SD values for first and repeat studies were almost identical: the 95% confidence interval of the mean test–retest difference was 0.055 to 0.076. Bland–Altman plots showed no systematic effect of the H/M ratio on the magnitude of the difference between replicate measurements. Inter-reader measurements were nearly identical. There were no serious adverse events despite exposure to 123I-mIBG on 2 occasions in a short time period. The Heart-to-Mediastinum ratio of 123I-mIBG is a consistent and highly reproducible measurement in stable Class II to III heart failure patients.

It is reported that pharmacokinetics after intravenous injection of 123I-ioflupane may reflect cerebral blood flow. In this study, the early-phase pharmacokinetics of 123I-ioflupane in 10 healthy volunteers was analyzed over time using dynamic single-photon emission computed tomography (SPECT) immediately after intravenous injection. We also examined the correlation between the 123I-IMP imaging and the 123I-ioflupane early-phase image for 14 cases in which both dopamine transporter (DaT) imaging by 123I-ioflupane and cerebral blood flow imaging by 123I-IMP were performed on the same camera. The time-activity curve between cerebellum (CBL) area and each area of anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA) showed distribution characteristics similar to 123I-IMP from immediately after intravenous injection until 20 minutes after administration, and there was no conspicuous washout. The regression line and the correlation coefficient of the Z-score of three-dimensional stereotactic surface projections (3DSSP) (decrease) of the early-phase imaging of 123I-ioflupane and the 123I-IMP imaging are y=0.7546x+0.3562, r=0.8169 (P

Information on the relationship between myocardial damage assessed by myocardial scintigraphy and prognosis in patients with Anderson–Fabry disease (AFD) is lacking. We therefore aimed to investigate the prognostic impacts of myocardial thallium-201 (201Tl) and iodine-123 beta-methyl 15-para-iodophenyl 3(R, S)-methylpentadecanoic acid (123I-BMIPP) dual scintigraphy in patients with AFD. Eighteen consecutive patients with AFD underwent resting myocardial 201Tl/123I-BMIPP dual scintigraphy. Total defect scores (TDS) on both images were calculated visually according to the 17-segment model using a 5-point scoring system. The mismatch score (MS) was calculated as ‘TDS on 123I-BMIPP—TDS on 201Tl’. Six major adverse cardiac events (MACEs) were recorded during a mean follow-up of 6.7 ± 4.2 years (three heart failure requiring hospitalization and three cardiac deaths). Left ventricular mass index, left atrial diameter, brain natriuretic peptide, TDS on 123I-BMIPP, and MS were all significantly greater in patients with MACEs compared with those without. Kaplan–Meier analysis indicated that high TDS on 123I-BMIPP and high MS were associated with poor event-free survival. TDS on 123I-BMIPP was a better prognostic determinant in patients with AFD than TDS on 201Tl. Myocardial 201Tl/123I-BMIPP dual scintigraphy may thus be a useful noninvasive modality for evaluating prognosis in patients with AFD.

123I-labeled meta-iodobenzylguanidine (MIBG) has used a planar image to measure the heart-to-mediastinum ratio (HMR). However, planar images are not available from IQ-SPECT with SMARTZOOM collimator due to its multi-focal collimation. Since we created the planar-equivalent (IQ-planar) images by adding all slices of the IQ-SPECT coronal image. The aim of this study was to demonstrate the utility of the new method for calculating HMR. The planar image and transverse images of IQ-SPECT with attenuation and scatter corrections (ACSC) and without ACSC (NC) were obtained. Multi-planar reconstruction and ray-summation processing were applied to create IQ-planar images with NC and ACSC. Linear regression between the measured HMR from the planar image and the mathematically calculated HMR was used to calibrate HMR to standardized values. Scatterplots and linear regression lines between planar and IQ-planar HMRs before and after cross-calibration showed systematic differences in both NC and ACSC conditions. The IQ-planar HMR with NC and ACSC was significantly higher compared with that of the conventional planar image. However, the IQ-planar HMR with NC and ACSC after cross-calibration was similar to the standardized HMR calculated by planar image. The IQ-planar HMR using the new ray-summation processing method could be used along with the conventional planar HMR.

Introduction: The choice of the radionuclide has a key role in nuclear medicine which appearing the lowest scatter fraction. In addition, the presence of penetrated and scattered photons from collimator in single-photon emission computed tomography images degrades resolution and contrast. Thus, image quality depends on sensitivity and resolution of the collimator–detector system. The goal of this study was to compare the image quality that can be achieved by three radionuclides: technetium-99 m (Tc-99 m), iodine-123 (I-123), and samarium-153 (Sm-153). Materials and Methods: Tc-99 m and Sm-153 were imaged with low-energy high resolution (LEHR) collimator, while I-123 was imaged with medium-energy (ME) collimator. We modeled the Siemens Symbia Medical system using Monte Carlo simulation code SIMIND. The imaging characteristics of each radionuclide were investigated by simulated data: point spread function, sensitivity (Cps/MBq) and geometric, penetration and scattering distribution. Results: Tc-99 m and Sm-153 give best and results with LEHR collimator for spatial resolution (full width at half maximum [FWHM] = 3.19 mm; full width at tenth maximum [FWTM] = 6.73 mm) and (FWHM = 3.22 mm; FWTM = 7.39 mm), respectively. Whereas, I-123 provided with ME collimator a lower resolution (FWHM = 4.89 mm; FWTM = 9.89 mm). The sensitivity recorded by Tc-99 m, Sm-153, and I-153 were (31.21 Cps/MBq), (10.16 Cps/MBq), and (51.22 Cps/MBq), respectively. Conclusion: Tc-99 m and Sm-153 give the best and generally similar imaging properties with LEHR. For I-123, the ME collimator helps lowering the influence of high-energy gamma rays.

Multi-pinhole (MPH) collimators are known to provide better trade-off between sensitivity and resolution for preclinical, as well as for smaller regions in clinical SPECT imaging compared to conventional collimators. In addition to this geometric advantage, MPH plates typically offer better stopping power for penetration than the conventional collimators, which is especially relevant for I-123 imaging. The I-123 emits a series of high-energy (>300 keV, similar to 2.5% abundance) gamma photons in addition to the primary emission (159 keV, 83% abundance). Despite their low abundance, high-energy photons penetrate through a low-energy parallel-hole (LEHR) collimator much more readily than the 159 keV photons, resulting in large downscatter in the photopeak window. In this work, we investigate the primary, scatter, and penetration characteristics of a single pinhole collimator that is commonly used for I-123 thyroid imaging and our two MPH collimators designed for I-123 DaTscan imaging for Parkinson's Disease, in comparison to three different parallel-hole collimators through a series of experiments and Monte Carlo simulations. The simulations of a point source and a digital human phantom with DaTscan activity distribution showed that our MPH collimators provide superior count performance in terms of high primary counts, low penetration, and low scatter counts compared to the parallel-hole and single pinhole collimators. For example, total scatter, multiple scatter, and collimator penetration events for the LEHR were 2.5, 7.6 and 14 times more than that of MPH within the 15% photopeak window. The total scatter fraction for LEHR was 56% where the largest contribution came from the high-energy scatter from the back compartments (31%). For the same energy window, the total scatter for MPH was 21% with only 1% scatter from the back compartments. We therefore anticipate that using MPH collimators, higher quality reconstructions can be obtained in a substantially shorter acquisition time for I-123 DaTscan and thyroid imaging.

The SEL-I-METRY trial (EudraCT No 2015-002269-47) is the first multicentre trial to investigate the role of 123I and 131I SPECT/CT-based tumour dosimetry to predict response to radioiodine therapy. Standardised dosimetry methodology is essential to provide a robust evidence-base for absorbed dose–response thresholds for molecular radiotherapy (MRT). In this paper a practical standardised protocol is used to establish the first network of centres with consistent methods of radioiodine activity quantification. Nine SPECT/CT systems at eight centres were set-up for quantitative radioiodine imaging. The dead-time of the systems was characterised for up to 2.8 GBq 131I. Volume dependent calibration factors were measured on centrally reconstructed images of 123I and 131I in six (0.8–196 ml) cylinders. Validation of image quantification using these calibration factors was performed on three systems, by imaging a 3D-printed phantom mimicking a patient’s activity distribution. The percentage differences between the activities measured in the SPECT/CT image and those measured by the radionuclide calibrator were calculated. Additionally uncertainties on the SPECT/CT-based activities were calculated to indicate the limit on the quantitative accuracy of this method. For systems set-up to image high 131I count rates, the count rate versus activity did not peak below 2.8 GBq and fit a non-paralysable model. The dead-times and volume-dependent calibration factors were comparable between systems of the same model and crystal thickness. Therefore a global calibration curve could be fitted to each. The errors on the validation phantom activities’ were comparable to the measurement uncertainties derived from uncertainty analysis, at 10% and 16% on average for 123I and 131I respectively in a 5 cm sphere. In conclusion, the dead-time and calibration factors varied between centres, with different models of system. However, global calibration factors may be applied to the same system model with the same crystal thickness, to simplify set-up of future multi-centre MRT studies.

Potentially false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma can mimic functioning thyroid tissue and functioning thyroid carcinomatous tissue. Such false-positive findings comprise variants and pitfalls that can vary slightly in children as compared with adults. To determine the patterns and frequency of these potential false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma. We reviewed a total of 223 radioiodine scans from 53 pediatric patients (mean age 13.3 years, 37 girls) with differentiated thyroid carcinoma. Focal or regional activity that likely did not represent functioning thyroid tissue or functioning thyroid carcinomatous tissue were categorized as variants or pitfalls. The final diagnosis was confirmed by reviewing the concurrent and follow-up clinical data, correlative ultrasonography, CT scanning, serum thyroglobulin and antithyroglobulin antibody levels. We calculated the frequency of these variants and pitfalls from diagnostic and post-therapy radioiodine scans. The most common variant on the radioiodine scans was the thymic activity (24/223, 10.8%) followed by the cardiac activity (8/223, 3.6%). Salivary contamination and star artifact, caused by prominent thyroid remnant, were the most important observed pitfalls. Variants and pitfalls that mimic functioning thyroid tissue or functioning thyroid carcinomatous tissue on radioiodine scan in children with differentiated thyroid carcinoma are not infrequent, but they decrease in frequency on successive radioiodine scans. Potential false-positive findings can be minimized with proper knowledge of the common variants and pitfalls in children and correlation with clinical, laboratory and imaging data.

Objectives The study sought to investigate adrenergic activity in patients with takotsubo cardiomyopathy (TTC). Background TTC is a specific type of reversible heart failure possibly caused by excessive catecholamine stimulation of the myocardium. Scintigraphic iodine-123– meta -iodobenzylguanidine ( m IBG) imaging of the heart and measurement of plasma catecholamines can be used to assess adrenergic activity in vivo. The authors hypothesized that sympathetic nerve activity is increased in the subacute state of TTC, and this study used cardiac m IBG imaging and plasma levels of norepinephrine and epinephrine as markers to assess this hypothesis. Methods In this study, 32 patients with TTC and 20 controls were examined at admission and again on follow-up with echocardiography, m IBG scintigraphy, and plasma catecholamine measurements. Results Ejection fraction (EF) was initially 36 ± 9% but increased to >60% (p = 0.0004) in all patients with TTC. In the control subjects EF was initially higher (51 ± 11%; p = 0.0004) than in the patients with TTC. However, EF of the patients with TTC exceeded that of the control subjects on follow-up (56 ± 8%; p = 0.0007). The m IBG imaging showed a lower late (4-h) heart-to-mediastinum ratio (H/M late ) (2.00 ± 0.38) and a higher washout rate (WR) (45 ± 12%) in the subacute state of TTC, both when compared with follow-up (H/M late : 2.42 ± 0.45; p = 0.0004; WR: 33 ± 14%; p = 0.0004) and when compared with the control group in the subacute state (H/M late : 2.34 ± 0.60, p = 0.035; WR: 33 ± 19%, p = 0.026). On follow-up, no differences in m IBG parameters were observed between the TTC and control groups (H/M late : 2.41 ± 0.51, p = 0.93; WR: 30 ± 13%, p = 0.48) group. In the TTC group, plasma epinephrine levels were elevated in the subacute state (Log 2 [epinephrine]: 6.13 ± 1.04 pg/ml), both when compared with follow-up (5.25 ± 0.62 pg/ml; p = 0.0004) and when compared with the control group in the subacute state (5.46 ± 0.69 pg/ml; p = 0.044), and these levels remained elevated in the TTC group on follow-up compared with the control group (4.56 ± 0.95 pg/ml; p = 0.014). No significant differences in plasma norepinephrine levels were observed. Conclusions The present study supports a possible role of adrenergic hyperactivity in TTC.

Imaging agents that target adenosine type 2A (A2A ) receptors play an important role in evaluating new pharmaceuticals targeting these receptors, such as those currently being developed for the treatment of movement disorders like Parkinson's disease. They are also useful for monitoring progression and treatment efficacy by providing a noninvasive tool to map changes in A2A receptor density and function in neurodegenerative diseases. We previously described the successful evaluation of two A2A -specific radiotracers in both nonhuman primates and in subsequent human clinical trials: [(123) I]MNI-420 and [(18) F]MNI-444. Herein we describe the development of both of these radiotracers by selection from a series of A2A ligands, based on the pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine core of preladenant. Each of this series of 16 ligands was found to bind to recombinant human A2A receptor in the low nanomolar range, and of these 16, six were radiolabeled with either fluorine-18 or iodine-123 and evaluated in nonhuman primates. These initial in vivo results resulted in the identification of 7-(2-(4-(4-(2-[(18) F]fluoroethoxy)phenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine ([(18) F]MNI-444) and 7-(2-(4-(2-fluoro-4-[(123) I]iodophenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-imidazo[1,2-c]pyrazolo[4,3-e]pyrimidin-5-amine ([(123) I]MNI-420) as PET and SPECT radiopharmaceuticals for mapping A2A receptors in brain.

Cardiac autonomic innervation plays an important role in regulating function. Adrenergic innervation imaging is possible with the norepinephrine analogue radiotracer iodine 123 meta-iodobenzylguanidine ((123)I-mIBG) and positron emitting tracers such carbon-11 hydroxyephedrine. (123)I-mIBG uptake is assessed globally via the heart to mediastinum ratio on planar images and regionally with tomographic imaging and has utility in various cardiac diseases. There is promise for guiding expensive invasive therapies such as implantable defibrillators, ventricular assist devices, and transplant. There are reports of utility in primary arrhythmic conditions, ischemic heart disease, and diabetes and after cardiac damaging chemotherapy.

Purpose The aim of this study was to investigate whether performing the late cardiac 123I-metaiodobenzylguanidine (MIBG) scan earlier than 4 h post-injection (p.i.) has relevant impact on the late heart to mediastinum ratio (H/M ratio) in patients with heart failure (HF). Methods Forty-nine patients with HF (median left ventricular ejection fraction of 31 %, 51 % ischaemic HF) referred for cardiac 123I-MIBG scintigraphy were scanned at 15 min (early) p.i. and at 1, 2, 3 and 4 h (late) p.i. of 123I-MIBG. Late H/M ratios were calculated and evaluated using a linear mixed model with the mean late H/M ratio at 4 h p.i. as a reference. A difference in late H/M ratios of more than 0.10 between the different acquisition times in comparison with the late H/M ratio at 4 h p.i. was considered as clinically relevant. Results Statistically significant mean differences were observed between the late H/M ratios at 1, 2 and 3 h p.i. compared with the late H/M ratio at 4 h p.i. (0.09, 0.05 and 0.02, respectively). However, the mean differences did not exceed the cut-off value of 0.10. On an individual patient level, compared to the late H/M ratio at 4 h p.i., the late H/M ratios at 1, 2 and 3 h p.i. differed more than 0.10 in 24 (50 %), 9 (19 %) and 2 (4 %) patients, respectively. Conclusion Variation in acquisition time of 123I-MIBG between 2 and 4 h p.i. does not lead to a clinically significant change in the late H/M ratio. An earlier acquisition time seems to be justified and may warrant a more time-efficient cardiac 123I-MIBG imaging protocol.

Purpose: A dedicated cardiac hybrid single photon emission computed tomography (SPECT)/CT scanner that uses cadmium zinc telluride detectors and multiple pinhole collimators for stationary acquisition offers many advantages. However, the impact of the reconstruction system matrix (SM) dimension on the reconstructed image quality from truncated projections and 19 angular samples acquired on this scanner has not been extensively investigated. In this study, the authors aimed to investigate the impact of the dimensions of SM and the use of body contour derived from adjunctive CT imaging as an object support in reconstruction on this scanner, in relation to background extracardiac activity. Methods: The authors first simulated a generic SPECT/CT system to image four NCAT phantoms with various levels of extracardiac activity and compared the reconstructions using SM in different dimensions and with/without body contour as a support for quantitative evaluations. The authors then compared the reconstructions of 18 patient studies, which were acquired on a GE Discovery NM570c scanner following injection of different radiotracers, including 99mTc-Tetrofosmin and 123I-mIBG, comparing the scanner's default SM that incompletely covers the body with a large SM that incorporates a patient specific full body contour. Results: The simulation studies showed that the reconstructions using a SM that only partially covers the body yielded artifacts on the edge of the field of view (FOV), overestimation of activity and increased nonuniformity in the blood pool for the phantoms with higher relative levels of extracardiac activity. However, the impact on the quantitative accuracy in the high activity region, such as the myocardium, was subtle. On the other hand, an excessively large SM that enclosed the entire body alleviated the artifacts and reduced overestimation in the blood pool, but yielded slight underestimation in myocardium and defect regions. The reconstruction using the larger SM with body contour yielded the most quantitatively accurate results in all the regions of interest for a range of uptake levels in the extracardiac regions. In patient studies, the SM incorporating patient specific body contour minimized extracardiac artifacts, yielded similar myocardial activity, lower blood pool activity, and subsequently improved myocardium-to-blood pool contrast (p < 0.0001) by an average of 7% (range 0%–18%) across all the patients, compared to the reconstructions using the scanner's default SM. Conclusions: Their results demonstrate that using a large SM that incorporates a CT derived body contour in the reconstruction could improve quantitative accuracy within the FOV for clinical studies with high extracardiac activity.

The predictors of outcome in patients with de novo diagnosis of heart failure (HF) with reduced ejection fraction (HFrEF) are poorly known. All consecutive HFrEF patients admitted between October 2012 and November 2017 with their first episode of HF were scheduled for an outpatient follow-up. After 3 months, patients with confirmed HFrEF underwent Iodine-123 Meta-Iodobenzylguanidine imaging. We defined three study endpoints: HF rehospitalization, cardiac death and all-cause death. Eighty-four patients were enrolled. During follow-up (39.9 ± 18.6 months) HF rehospitalization occurred in 33 cases, cardiac death in 18 and all-cause death in 24. At multivariate analysis, systolic pulmonary arterial pressure (sPAP; HR: 1.047; p = .027) and Late lung to heart ratio (L/H; HR: 1.341; p

The aim of this study was to study the significance of combining iodine-123-cardiac metaiodobenzylguanidine scintigraphy (I-MIBG scintigraphy) and iodine-123-ioflupane (I-ioflupane) dopamine transporter scintigraphy (I-ioflupane scintigraphy) in patients suspected of having Parkinson's disease (PD).We carried out a retrospective study from April 2014 to December 2015 in 48 patients suspected of having new-onset PD who underwent both I-MIBG and I-ioflupane scintigraphies within 3 months. Cases included 37 patients diagnosed as having PD. Controls included 11 patients who had never been diagnosed as having PD or other diseases showing parkinsonism. The cutoff for diagnosing PD was a heart to mediastinum ratio (H/M ratio) of less than or equal to 2.2 for I-MIBG scintigraphy in the delayed phase and a specific binding ratio (SBR) of less than or equal to 3.8 for I-ioflupane scintigraphy. The combined use of both scintigraphies was studied using the formula SBR×H/M ratio as a marker for the logistic regression model.Sixteen (33.3%) patients had SBR of greater than 3.8: eight with PD; eight were controls. Five of eight patients had an H/M ratio of less than or equal to 2.2 (62.5%) and had PD. In the receiver-operating characteristic analysis, the SBR×H/M ratio cutoff was 12.5, with an area under the curve of 0.844 (95% confidence interval: 0.619-1). In an age-adjusted regression analysis in patients with SBR of greater than 3.8, the SBR×H/M ratio was associated significantly with an odds ratio of 0.69 (95% confidence interval: 0.48-0.98, P=0.041).If SBR is greater than 3.8, the SBR×H/M ratio can help diagnose PD. The combined use of the two scintigraphies can improve the diagnosis of PD.

Background ― Cadmium zinc telluride (CZT) solid-state detectors have been recently introduced in the field of nuclear medicine in cardiology. The aim of the current study was to investigate the scintigraphic patterns of total uptake and the regional distribution of iodine-123 metaiodobenzylguanidine (123I-mIBG) in healthy volunteers and patients with atrial fibrillation (AF) using a gamma camera equipped CZT detectors. Material and Methods ― The total number of included subjects was 30 (15 patients with a paroxysmal form of AF and 15 healthy volunteers). Using a novel single-photon emission computed tomography (SPECT) cardiac dedicated gamma camera equipped CZT-detectors the scintigraphy was performed 15 minutes and 4 hours after intravenous administration of norepinephrine structural analogue 123I-mIBG. Thus, data from early and delayed phases were obtained. The heart-to-mediastinum ratio of 123I-mIBG uptake at 15 minutes (HMRe) and 4 hours (HMRd), as well as the washout rate (WR) and summed 123I-mIBG score (SMSe, SMSd) were measured. Results ― Patients and volunteers showed comparable results of the median ratio of 123I-mIBG uptake in the heart and mediastinum (HMR) in the early and delayed phases (p>0.05). In 14 (93%) patients with AF, 123I-mIBG uptake defects in LV myocardium were detected as compared with 8 (53%) healthy individuals (p

金沢大学医薬保健研究域保健学系, ObjectivesAlthough the utility of IQ-SPECT imaging using 99mTc and 201Tl myocardial perfusion SPECT has been reported, 123I-labeled myocardial SPECT has not been fully evaluated. We determined the characteristics and utility of 123I IQ-SPECT imaging compared with conventional SPECT (C-SPECT).MethodsTwo myocardial phantom patterns were used to simulate normal myocardium and myocardial infarction. SPECT acquisition was performed using a hybrid dual-head SPECT/CT system equipped with a SMARTZOOM collimator for IQ-SPECT or a low-medium energy general purpose collimator for C-SPECT. Projection data were reconstructed using ordered subset expectation maximization with depth-dependent 3-dimensional resolution recovery for C-SPECT and ordered subset conjugate gradient minimizer method for IQ-SPECT. Three types of myocardial image were created; namely, no correction (NC), with attenuation correction (AC), and with both attenuation and scatter corrections (ACSC). Five observers visually scored the homogeneity of normal myocardium and defect severity of the myocardium with inferior defects by a five-point scale: homogeneity scores (5 = homogeneous to 1 = inhomogeneous) and defect scores (5 = excellent to 1 = poor). We also created a 17-segment polar map and quantitatively assessed segmental %uptake using a myocardial phantom with normal findings and defects.ResultsThe average visual homogeneity scores of the IQ-SPECT with NC and ACSC were significantly higher than that of C-SPECT, whereas the average visual defect scores of IQ-SPECT with AC and ACSC were significantly lower. The %uptake of all segments for IQ-SPECT with NC was significantly higher than that of C-SPECT. Furthermore, the subtraction of %uptake for C-SPECT and IQ-SPECT was the largest in inferior wall, which was approximately 10.1%, 14.7% and 14.4% for NC, AC and ACSC, respectively. The median % uptake values of the inferior wall with defect areas for C-SPECT and IQ-SPECT were 46.9% and 50.7% with NC, 59.8% and 69.2% with AC, and 54.7% and 66.5% with ACSC, respectively.Conclusion123I IQ-SPECT imaging significantly improved the attenuation artifact compared with C-SPECT imaging. Although the defect detectability of IQ-SPECT was inferior to that of C-SPECT, 123I IQ-SPECT images with NC and ACSC met the criteria for defect detectability. Use of 123I IQ-SPECT is suitable for routine examinations., Embargo Period 12 months

BACKGROUND Myocardial salvage is an important surrogate endpoint to estimate the impact of treatments in patients with ST-segment elevation myocardial infarction (STEMI). AIM The aim of this study was to evaluate the correlation between cardiac sympathetic denervation area assessed by single-photon emission computed tomography (SPECT) using iodine-123-meta-iodobenzylguanidine (I-MIBG) and myocardial area at risk (AAR) assessed by cardiac magnetic resonance (CMR) (gold standard). PATIENTS AND METHODS A total of 35 postprimary reperfusion STEMI patients were enrolled prospectively to undergo SPECT using I-MIBG (evaluates cardiac sympathetic denervation) and thallium-201 (evaluates myocardial necrosis), and to undergo CMR imaging using T2-weighted spin-echo turbo inversion recovery for AAR and postgadolinium T1-weighted phase sensitive inversion recovery for scar assessment. RESULTS I-MIBG imaging showed a wider denervated area (51.1±16.0% of left ventricular area) in comparison with the necrosis area on thallium-201 imaging (16.1±14.4% of left ventricular area, P

The washout rate (WR) has been used in (123)I-metaiodobenzylguanidine (MIBG) imaging to evaluate cardiac sympathetic innervation. However, WR varies depending on the time between the early and late MIBG scans. Late scans are performed at either 3 or 4 hours after injection of MIBG. The aim of this study was to directly compare the WR at 3 hours (WR3h) with the WR at 4 hours (WR4h).We hypothesized that the cardiac count would reduce linearly between the 3-hour and 4-hour scans. A linear regression model for cardiac counts at two time-points was generated. We enrolled a total of 96 patients who underwent planar (123)I-MIBG scintigraphy early (15 min) and during the late phase at both 3 and 4 hours. Patients were randomly divided into two groups: a model-creation group (group 1) and a clinical validation group (group 2). Cardiac counts at 15 minutes (countearly), 3 hours (count3h) and 4 hours (count4h) were measured. Cardiac count4h was mathematically estimated using the linear regression model from countearly and count3h.In group 1, the actual cardiac count4h/countearly was highly significantly correlated with count3h/countearly (r = 0.979). In group 2, the average estimated count4h was 92.8 ± 31.9, and there was no significant difference between this value and the actual count4h (91.9 ± 31.9). Bland-Altman analysis revealed a small bias of -0.9 with 95 % limits of agreement of -6.2 and +4.3. WR4h calculated using the estimated cardiac count4h was comparable to the actual WR4h (24.3 ± 9.6 % vs. 25.1 ± 9.7 %, p = ns). Bland-Altman analysis and the intraclass correlation coefficient showed that there was excellent agreement between the estimated and actual WR4h.The linear regression model that we used accurately estimated cardiac count4h using countearly and count3h. Moreover, WR4h that was mathematically calculated using the estimated count4h was comparable to the actual WR4h.

The objectiveof this study is to assess perfusion and metabolic state of the left ventricular in patients with dilated cardiomyopathy (DCM) using scintigraphy with MIBI and BMIPP, as well as to develop the predictors of efficacy of cardiac resynchronization therapy (CRT). The study included 51 patients with DCM who underwent CRT. Correlation between the values of LV ESV after CRT and preoperative perfusion and metabolic defects sizes was detected. "Responders" and "non-responders" groups were significantly different from the perfusion and metabolic defects sizes. Myocardial perfusion-metabolic scintigraphy can be used as additional criteria for the selection of patients for CRT.

This paper demonstrates a method for production of the radiopharmaceutical meta-iodobenzilguanidin (MIBG) labeled with radionuclide iodine-123 (123I). An experimental installation has been developed and the conditions of solid-phase synthesis of the preparation have been described. The influence of the content of ammonium sulfate in the reaction mixture and the temperature and duration of dry synthesis on the process of labeling has been researched. It has been established experimentally that when the ratio of MIBG and ammonium sulfate is 1:4, it is efficient to carry out synthesis at the temperature of 150°C to rapidly obtain a preparation with radiochemical purity of over 97%. Biomedical tests of the synthesized preparation have been carried out in experimental animals. Its functional suitability for scintigraphic studies has been shown.

Pure autonomic failure is challenging as it can be the presenting feature of a central nervous system syncleinopathy such as Parkinson’s disease (PD) or multiple system atrophy (MSA). Because the prognosis of MSA and PD is so different, predictive features for a possible conversion can be extremely valuable. In this paper, we report three cases (two with autopsy-proven diagnosis) that had isolated AF for many years before converting to MSA or PD. Of all the tests that were performed during the premotor stage, Iodine-123-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy was predictive of the conversion to MSA. We suggest that MIBG myocardial scintigraphy, when performed in patients with isolated AF, may be a valuable predictor of conversion to MSA. On the contrary, the role of such test in parkinsonian patients irrespective of the presence of AF is still to be clarified.

Cardiac sympathetic nervous activity can be uniquely visualized by non-invasive radionuclide imaging techniques due to the fast growing and widespread application of nuclear cardiology in the last few years. The norepinephrine analogue 123I–meta-iodobenzylguanidine (123I–MIBG) is a single photon emission computed tomography (SPECT) tracer for the clinical implementation of sympathetic nervous imaging for both diagnosis and prognosis of heart failure. Meanwhile, positron emission tomography (PET) imaging has become increasingly attractive because of its higher spatial and temporal resolution compared to SPECT, which allows regional functional and dynamic kinetic analysis. Nevertheless, wider use of cardiac sympathetic nervous PET imaging is still limited mainly due to the demand of costly on-site cyclotrons, which are required for the production of conventional 11C-labeled (radiological half-life, 20 min) PET tracers. Most recently, more promising 18F-labeled (half-life, 110 min) PET radiopharmaceuticals targeting sympathetic nervous system have been introduced. These tracers optimize PET imaging and, by using delivery networks, cost less to produce. In this article, the latest advances of sympathetic nervous imaging using 18F-labeled radiotracers along with their possible applications are reviewed.

Antisense oligonucleotides (AONs) are promising candidates for treatment of Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in premature death. However, more knowledge on the pharmacokinetics of new AON drug candidates is desired for effective application in the clinic. We assessed the feasibility of using noninvasive single-photon emission computed tomography-computed tomography (SPECT-CT) imaging to determine AON pharmacokinetics in vivo. To this end, a 2'-O-methyl phosphorothioate AON was radiolabeled with 123I or 111In, and administered to mdx mice, a rodent model of DMD. SPECT-CT imaging was performed to determine AON tissue levels, and the results were compared to data obtained with invasive analysis methods (scintillation counting and a ligation-hybridization assay). We found that SPECT-CT data obtained with 123I-AON and 111In-AON were qualitatively comparable to data derived from invasive analytical methods, confirming the feasibility of using SPECT-CT analysis to study AON pharmacokinetics. Notably, also AON uptake in skeletal muscle, the target tissue in DMD, could be readily quantified using SPECT-CT imaging, which was considered a particular challenge in mice, due to their small size. In conclusion, our results demonstrate that SPECT-CT imaging allows for noninvasive characterization of biodistribution and pharmacokinetics of AONs, thereby enabling quantitative comparisons between different radiolabeled AON drug candidates and qualitative conclusions about the corresponding unmodified parent AONs. This technology may contribute to improved (pre)clinical drug development, leading to drug candidates with optimized characteristics in vivo.

The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells, 123I-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An 123I-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC50 of 1.58 μM (MST-312 IC50: 0.23 μM). Clonogenic assays showed a dose dependant effect of 123I-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435., Graphical abstract Image 1, Highlights • 123I-radiolabeled small molecule inhibitors of telomerase were synthesized. • Synchronous telomerase inhibition and radionuclide therapy was achieved. • 123I-MST-312 caused cytotoxicity in telomerase positive cancer cells.

Background Nuclear myocardial imaging with iodine-123 meta-iodobenzylguanidine ( 123 I- m IBG) is approved for risk stratification of patients with systolic heart failure (HF). Whether 123 I- m IBG imaging provides incremental prognostic utility beyond established risk models remains unclear. Methods and Results In a multicenter study, 961 patients with moderate systolic HF underwent 123 I- m IBG imaging and were followed for cardiac death, progressive HF, or life-threatening arrhythmias over 2 years. We constructed 4 multivariable models, using variables from each of 4 published HF risk models, and patient-level scores were calculated both before and after adding the heart-to-mediastinum ratio (H/M) from 123 I- m IBG imaging. Incremental utility was evaluated by calculating integrated discrimination improvement (IDI), which quantifies the increase in probability of experiencing the primary end point after adding H/M to each model. The composite end point occurred in 25% of patients. After adding H/M, absolute IDI ranged from 2.1% to 3.0%, representing 33%–59% relative improvements in risk stratification. Of note, hazard ratios for H/M were remarkably similar between risk models (0.40–0.44 for predicting the composite end point, 0.10–0.18 for mortality; all P Conclusions Despite notable differences in predictor variables, patient populations, and analytic techniques from which each model was initially derived, adding 123 I- m IBG data to HF risk models consistently identified patients at lower risk of experiencing adverse events.

The phenyl-amino-thiazole (PAT) templates of methoxylbenzoyl-aryl-thiazole are potent agents against cancer by inhibiting tubulin polymerization in the nanomolar range. Herein, a radioiodinated PAT, [(123)I]-PAT 1, was prepared via a tributylstannyl precursor and [(123)I]iodide through electrophilic aromatic radioiodination. Radiolabelling of [(123)I]-PAT 1 was achieved in less than 15 min, with a radiochemical purity of over 99%. The accumulated radioactivity in tumor cellular uptake experiments suggested that [(123) I]-PAT could serve as a potential radioprobe for targeting tumor cells.

OBJECTIVE We compared cerebral blood flow (CBF) measured using computed tomographic (CT) perfusion (CTP) and N-isopropyl-p-[(123) I]-iodoamphetamine cerebral perfusion single-photon emission computed tomography (SPECT). METHODS We used a 320-row area detector CT and N-isopropyl-p-[(123) I]-iodoamphetamine cerebral perfusion SPECT under similar conditions in patients with chronic cerebrovascular disease. Images were automatically aligned 3-dimensionally for voxel-by-voxel comparisons. RESULTS Linear positive correlations were observed between CTP-CBF including high-blood-flow areas and SPECT-CBF over the whole brain (r = 0.001-0.6, P < 0.01), superior cerebral level (r = 0.45-0.93, P < 0.01), basal ganglia level (r = 0.44-0.77, P < 0.01), and skull base (r = 0.02-0.66, P < 0.01). Correlations between CTP-CBF excluding high-blood-flow areas were significantly higher (P < 0.0001). CONCLUSIONS Computed tomographic perfusion overestimated CBF compared with SPECT and showed poor correlation at the skull base. Computed tomographic perfusion CTP excluding high-blood-flow areas improved the correlation over the whole brain in patients with chronic cerebrovascular disease.

Iodine-123 meta-iodobenzylguanidine (I-mIBG) imaging has prognostic value in patients with heart failure (HF). Renal dysfunction is prevalent in HF patients. I-mIBG is excreted by the kidneys, and the effect of renal dysfunction on its myocardial uptake and established prognostic value in HF patients is unknown.The data analysed are from patients with New York Heart Association (NYHA) class II or III HF enrolled in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study. Myocardial uptake and retention of I-mIBG were assessed by the early and late heart-to-mediastinal (HM) ratio. Effect of renal dysfunction on the prognostic value of I-mIBG was determined by multivariable-predicted survival analysis stratified by glomerular filtration rate (GFR) and late HM ratio. Cox proportional hazard models were used to determine the predictors of cardiac events (CEs, defined as death, HF progression or life-threatening arrhythmia).Complete data were available on 867 patients. The GFR range was 19-140 ml/min, and 344 (40%) patients had renal dysfunction (GFR60 ml/min). A total of 523 (60%) and 689 (80%) patients had early and late HM ratios below the previously established prognostic cutoff of 1.6. There was no relationship between early or late HM ratios and GFR after controlling for HF severity (NYHA class and norepinephrine levels), indicating a lack of effect of renal dysfunction on the HM ratio. Significant independent predictors of CE were (hazard ratio, P), b-type natriuretic peptide level (1.4,0.001), left ventricular ejection fraction (0.95,0.001), BMI (1.04, 0.002), cardiac glycoside use (1.42, 0.019) and late HM ratio (7.04, 0.008). Neither GFR nor its interaction with late HM ratio was a significant predictor of CE.Renal dysfunction does not affect the HM ratios or the prognostic value of I-mIBG imaging in HF patients.

Introduction O -(2-[ 18 F]fluoroethyl)-l-tyrosine (FET, [ 18 F] 1 ) is a useful amino-acid-based imaging agent for brain tumors. This paper reports the synthesis and evaluation of three FET prodrugs, O -(2-[ 18 F]fluoroethyl)-l-tyrosyl-l-glycine (FET-Gly, [ 18 F] 2 ), O -(2-[ 18 F]fluoroethyl)-l-tyrosyl-l-alanine (FET-Ala, [ 18 F] 3 ) and N -acetyl O -(2-[ 18 F]fluoroethyl)-l-tyrosine (AcFET, [ 18 F] 4 ), which could be readily hydrolyzed to FET in vivo for tumor imaging. We investigated their metabolism in the blood and imaging properties in comparison to FET ([ 18 F] 1 ). Methods Three new [ 18 F]FET derivatives, 2 – 4 , were prepared from their corresponding tosylate-precursors through nucleophilic fluorination and subsequent deprotection reactions. In vitro uptake studies were carried out in 9L glioma cancer cell lines. In vitro and in vivo hydrolysis studies were conducted to evaluate the hydrolysis of FET prodrugs in blood and in Fisher 344 rats. Biodistribution and PET imaging studies were then performed in rats bearing 9L tumors. Results New FET prodrugs were prepared with 3–28% decay corrected radiochemical yields, good enantiomeric purity (>95%) and high radiochemical purity (>95%). FET-Gly ([ 18 F] 2 ), FET-Ala ([ 18 F] 3 ), and AcFET ([ 18 F] 4 ) exhibited negligible uptake in comparison to the high uptake of FET ([ 18 F] 1 ) in 9L cells. Metabolism studies of FET-Gly ([ 18 F] 2 ), FET-Ala ([ 18 F] 3 ), and AcFET ([ 18 F] 4 ) in rat and human blood showed that FET-Ala ([ 18 F] 3 ) was hydrolyzed to FET ([ 18 F] 1 ) faster than FET-Gly ([ 18 F] 2 ) or AcFET ([ 18 F] 4 ). Most of the FET-Ala (79%) was converted to FET ([ 18 F] 1 ) within 5min in blood in vivo . Biodistribution studies demonstrated that FET-Ala ([ 18 F] 3 ) displayed the highest tumor uptake. The tumor-to-background ratios of FET-Ala ([ 18 F] 3 ) and FET ([ 18 F] 1 ) were comparable and appeared to be better than those of FET-Gly ([ 18 F] 2 ) and AcFET ([ 18 F] 4 ). PET imaging studies showed that both FET ([ 18 F] 1 ) and FET-Ala ([ 18 F] 3 ) could visualize tumors effectively, and that they share similar imaging characteristics. Conclusions FET-Ala ([ 18 F] 3 ) demonstrated promising properties as a prodrug of FET ([ 18 F] 1 ), which could be used in PET imaging of tumor amino acid metabolism.

We investigated how the degree of cardiac uptakes of radioactive fatty acid (FA) analog ( 123 I-BMIPP) or norepinephrine (NE) analog ( 123 I-MIBG) was related to left ventricular (LV) functional parameters in patients with heart disease, which might be a predictor of cardiac events. Patients with ejection fraction (EF) of 16.2%-82.2% underwent 123 I-BMIPP or 123 I-MIBG myocardial scintigraphy, and were followed up over 1177±486 days. LV systolic functional parameter EF, diastolic parameters 1/3FR (first third filling rate), PFR (peak filling rate), and TPF (time to PFR) were calculated using quantitative gated SPECT. 123 I-BMIPP uptake (n=30) was significantly correlated with EF, 1/3FR, and PFR but not TPF. 123 I-MIBG uptake (n=37) was also correlated with EF, 1/3FR, and PFR but not TPF. In contrast, TPF was positively correlated with age, and was significantly longer in women than in men. Such findings were also observed in normal EF patients (≥50%, n=100). Kaplan–Meier analysis showed the occurrence of earlier cardiac events in the case of patients with decreased 123 I-BMIPP and 123 I-MIBG uptake, decreased PFR, and prolonged TPF. The degree of decreased cardiac uptakes of FA and NE may be associated with the grade of systolic and diastolic dysfunctions assessed by EF, PFR, and 1/3FR. In contrast, prolonged TPF, another diastolic parameter, may rather be caused by aging and female gender, independent of EF. Despite these differences, myocardial FA metabolism impairment, cardiac sympathetic nerve inactivity, decreased PFR, and prolonged TPF may all indicate poor cardiac prognosis in patients with heart disease. Keywords123 I-BMIPP; 123 I-MIBG; Cardiac Function; Heart Failure

Dopamine subtype 2 receptors (D2DRs) are overexpressed in pheochromocytomas (PHEOs). D2DR-expressing tumors can be visualized by iodine-123 labeled iodobenzamide (¹²³I-IBZM) single-photon emission computed tomography (SPECT).The hypothesis of this study was that D2DR high expression in PHEOs would allow in vivo visualization through ¹²³I-IBZM SPECT. The present prospective pilot study aims to evaluate the performance of ¹²³I-IBZM SPECT in PHEOs and to correlate the tumor uptake with D2DR expression in tumor samples after surgery. SETTING, MATERIALS, AND METHODS: Ten unrelated patients with PHEOs were evaluated, prior to adrenalectomy, with ¹²³I-IBZM SPECT (whole body scan at 4 and 24 h after the injection; and SPECT centered on the abdomen at 24 h). D2DR mRNA and protein expressions were evaluated in all tumors by quantitative real-time RT-PCR and immunohistochemistry, respectively.Intensity of tumoral uptake of ¹²³I-IBZM was measured.All PHEOs express D2DR mRNA (ranging from 2.1 to 14.7 copy/copy β-glucuronidase) and protein (immunostaining score: moderate or strong in 9 of 10 cases). However, none of the patients (0%) showed an increased tumor uptake of ¹²³I-IBZM.These results suggest that ¹²³I-IBZM is not a useful radiopharmaceutical in the detection and characterization of PHEOs despite D2DR expression. Our findings and data from the related literature may support different hypotheses to explain the failure of D2DR targeting by ¹²³I-IBZM.

This study evaluated a radioiodinated deoxycytidine analog, (131)I-5-iodo-2'-deoxycytidine ([(131)I]ICdR), as a novel proliferation probe and compared it with (131)I-5-iodo-2'-deoxyuridine ([(131)I]IUdR) in a NG4TL4 sarcoma-bearing mouse model. As an imaging agent, the biological characteristics of [(123)I]IUdR is not satisfactory due to its metabolic instability and short biological half-life in vivo. With [(123)I]ICdR/SPECT it was possible to clearly delineate the tumor lesion at 1h post-injection (tumor-to-muscle ratio 7.74) in tumor-bearing mice. The results of biodistribution were consistent with those observed in scintigraphic imaging. This study demonstrated that [(131)I]ICdR is a more promising SPECT probe than [(131)I]IUdR for imaging proliferation.

Aripiprazole was successfully labeled with radioactive iodine using chloramine-T via an electrophilic substitution reaction. The influence exerted on the labeling yield by reaction parameters such as concentration, pH, and time was studied to optimize the labeling conditions. The radiochemical yield was 96 ± 3%. The radioiodinated compound was separated by HPLC. In vitro studies showed that the compound was stable for up to 24 h. The brain uptake was 5.53%, which was higher than that for the commercially available Ceretec kit. The clearance from the rats occurs via the hepatobiliary and renal pathways. Predosing the rats with cold aripiprazole reduced the brain uptake to 1.9 ± 0.1% and further confirmed that the uptake of this radioiodinated compound was specific for the brain. A mechanism of the formation of electropositive iodine is discussed, and possible oxidizing species of Chloramine-T in both acidic and alkaline media are ascertained.

ObjectiveThe aim of the study was to assess the diagnostic performance of co-registered single photon emission computed tomography (SPECT)/computed tomography (CT) compared to Iodine-123 whole body gamma camera (WBGC) imaging and to SPECT alone in patients with differentiated thyroid cancer.MethodsWBGC and SPECT/CT (n=85) imaging of the neck and thorax was performed in 79 consecutive patients. Three experienced observers reviewed: i) WBGC images followed by ii) SPECT alone, and iii) co-registered SPECT/CT. Foci of increased radioiodine uptake were classified on a five-point scale. Biopsy, other imaging modalities, and clinical follow-up served as the reference standard.ResultsTwenty-two patients had local recurrence or metastatic thyroid cancer (11 were radioiodine negative), 9 had remnant thyroid tissue, and 54 had no evidence of disease. When classifying equivocal, probably, and definitely malignant findings as positive for malignancy, the sensitivity, specificity, positive predictive value, and negative predictive value were as follows: 41, 68, 31, and 77% for WBGC imaging; 45, 89, 59, and 82% for WBGC plus SPECT imaging; and 50, 100, 100, and 85% for WBGC plus SPECT/CT imaging respectively. The specificity was improved by the addition of SPECT (P=0.0002) and SPECT/CT (PP=0.016). In a study-based analysis, SPECT/CT provided additional diagnostic information in 42% (36/85) of cases. SPECT/CT provided further characterization in 70% (63/90) of foci and improved the diagnostic confidence of all three observers.ConclusionThe addition of SPECT/CT significantly improved the diagnostic information over Iodine-123 WBGC imaging and WBGC plus SPECT imaging alone.