Optimizing the pharmacokinetics of an 211At-labeled RGD peptide with an albumin-binding moiety via the administration of an albumin-binding inhibitor.

PURPOSE: A probe for targeted alpha therapy (TAT) using the RGD peptide (Ga-DOTA-K([211At]APBA)-c(RGDfK) ([211At]1)) with albumin-binding moiety (ABM) was recently developed. [211At]1 highly accumulated in tumors and significantly inhibited tumor growth in U-87 MG tumor-bearing mice. However, high [211At]1 retention in blood may cause critical adverse events, such as hematotoxicity. Therefore, we attempted to accelerate the blood clearance of [211At]1 by competitively inhibiting the binding of [211At]1 to albumin to modulate the pharmacokinetics of the former. METHODS: To evaluate the effects of albumin-binding inhibitors in normal mice, sodium 4-(4-iodophenyl)butanoate at 2, 5, or 10 molar equivalents of blood albumin was administered at 1-h postinjection of [211At]1. The biodistribution of [211At]1, SPECT/CT imaging of [67Ga]Ga-DOTA-K(IPBA)-c(RGDfK) ([67Ga]2), and the therapeutic effects of [211At]1 were compared with or without IPBA administration in U-87 MG tumor-bearing mice. RESULTS: Blood radioactivity of [211At]1 was decreased in a dose-dependent manner with IPBA in normal mice. In U-87 MG tumor-bearing mice, the blood radioactivity and accumulation in nontarget tissues of [211At]1 were decreased by IPBA. Meanwhile, tumor [211At]1 accumulation was not changed at 3-h postinjection of IPBA. In SPECT/CT imaging of [67Ga]2, IPBA administration dramatically decreased radioactivity in nontarget tissues, and only tumor tissue was visualized. In therapeutic experiments, [211At]1 with IPBA injected-group significantly inhibited tumor growth compared to the control group. CONCLUSION: IPBA administration (as an albumin-binding inhibitor) could modulate the pharmacokinetics and enhance the therapeutic effects of [211At]1.

Development of probes for radiotheranostics with albumin binding moiety to increase the therapeutic effects of astatine-211 (211At).

PURPOSE: We have developed probes for multiradionuclides radiotheranostics using RGD peptide ([67Ga]Ga-DOTA-c[RGDf(4-I)K] ([67Ga]1) and Ga-DOTA-[211At]c[RGDf(4-At)K] ([211At]2)) for clinical applications. The introduction of an albumin binding moiety (ABM), such as 4-(4-iodophenyl)-butyric acid (IPBA), that has high affinity with the blood albumin and prolongs the circulation half-life can improve the pharmacokinetics of drugs. To perform more effective targeted alpha therapy (TAT), we designed and synthesized Ga-DOTA-K([211At]APBA)-c(RGDfK) ([211At]5) with 4-(4-astatophenyl)-butyric acid (APBA), which has an astato group instead of an iodo group in IPBA. We evaluated whether APBA functions as ABM and [211At]5 is effective for TAT. In addition, we prepared 67Ga-labeled RGD peptide without ABM, [67Ga]Ga-DOTA-K-c(RGDfK) ([67Ga]3), and 125I-labeled RGD peptide with ABM, Ga-DOTA-K([125I]IPBA)-c(RGDfK) ([125I]4), to compare with [211At]5. METHODS: Biodistribution experiments of [67Ga]3 without ABM, [125I]4 and [211At]5 with ABM were conducted in normal mice and U-87 MG tumor-bearing mice. In addition, two doses of [211At]5 (370 or 925 kBq) were administered to U-87 MG tumor-bearing mice to confirm the therapeutic effects. RESULTS: The blood retention of [125I]4 and [211At]5 was remarkably increased compared to [67Ga]3. Also, [125I]4 and [211At]5 showed similar biodistribution and significantly greater tumor accumulation and retention compared to [67Ga]3. In addition, [211At]5 inhibited tumor growth in a dose-dependent manner. CONCLUSION: The functionality of APBA as ABM like IPBA, and the usefulness of [211At]5 as the radionuclide therapy agent for TAT was revealed.

Synthesis and Evaluation of Radiogallium Labeled Bone-Imaging Probes Using Oligo-γ-Carboxy Glutamic Acid Peptides as Carriers to Bone.

We investigated the importance of the carboxy group density in bone affinity during the development of peptide-based bone-seeking radiopharmaceuticals and carriers. Oligo-γ-carboxy glutamic acid peptides [(Gla)n] with higher carboxy group density than oligo-glutamic acid peptides [(Glu)n] and oligo-aspartic acid peptides [(Asp)n] were chosen. Using the radiogallium chelator N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC), we synthesized [67Ga]Ga-HBED-CC-(Gla)n (n = 1, 2, 5, 8, 11, or 14) with high yields. Hydroxyapatite-binding assays, biodistribution, and SPECT imaging showed higher affinity and bone accumulation for [67Ga]Ga-HBED-CC-(Gla)n compared to [67Ga]Ga-HBED-CC-(Glu)n. Notably, [67Ga]Ga-HBED-CC-(Gla)8 and [67Ga]Ga-HBED-CC-(Gla)11 exhibited superior bone accumulation and rapid blood clearance. SPECT/CT imaging with [67Ga]Ga-HBED-CC-(Gla)8 exclusively visualized the bone tissue. These findings support the potential use of [67Ga]Ga-HBED-CC-(Gla)n as excellent bone-imaging PET probes, suggesting (Gla)n peptides are superior bone-seeking carriers.

125I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (125I-OI5V) imaging visualized augmented sigma-1 receptor expression according to the severity of myocardial ischemia.

BACKGROUND: We aimed to explore how the severity of myocardial ischemia affects myocardial sigma-1 receptor (Sig-1R) expression using 125I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (125I-OI5V) imaging. METHODS AND RESULTS: The left coronary artery was occluded for 30, 20, and 10 minute, to vary the severity of myocardial ischemia, followed by reperfusion. Dual-tracer autoradiography of the left ventricular short-axis slices was performed 3 and 7 days after reperfusion. 125I-OI5V was injected 30 minute before sacrifice and the area at risk (AAR) was evaluated by 99mTc-MIBI. Intense 125I-OI5V uptake was observed in the AAR and was significantly increased with increasing ischemia duration. To evaluate salvaged and nonsalvaged areas (preserved and decreased perfusion areas), triple-tracer autoradiography was performed 3 days after reperfusion. After dual-tracer autoradiography, 201Tl was injected 20 minute post 125I-OI5V injection. On triple-tracer autoradiography, the AAR/normally perfused area 125I-OI5V uptake ratio was positively correlated with the nonsalvaged area/whole left ventricular (LV) area ratio (P < .05). The AAR/normally perfused area 125I-OI5V uptake ratio was negatively correlated with the 201Tl uptake ratio of the AAR to normally perfused areas (P < .05). The comparison of the immunostaining distribution of 125I-OI5V and the macrophage marker CD68 revealed that 125I-OI5V was present mainly in, and immediately adjacent to the macrophage infiltration area. CONCLUSIONS: Significant 125I-OI5V uptake in the AAR depends on the duration of ischemia and reduced 201Tl uptake; furthermore, 125I-OI5V was found in and around the macrophage infiltrate area. These results indicate that iodine-labeled OI5V is a promising tool for visualizing Sig-1R expression according to the ischemic burden.

Transthyretin amyloid cardiomyopathy disease burden quantified using 99mTc-pyrophosphate SPECT/CT: volumetric parameters versus SUVmax ratio at 1 and 3 hours.

BACKGROUND: Various parameters derived from technetium-99m pyrophosphate (99mTc-PYP) single-photon emission computed tomography (SPECT) correlate with the severity of transthyretin amyloid cardiomyopathy (ATTR-CM). However, the optimal metrics and image acquisition timing required to quantify the disease burden remain uncertain. METHODS AND RESULTS: We retrospectively evaluated 99mTc-PYP SPECT/CT images of 23 patients diagnosed with ATTR-CM using endomyocardial biopsies and/or gene tests. All patients were assessed by SPECT/CT 1 hour after 99mTc-PYP injection, and 13 of them were also assessed at 3 hours. We quantified 99mTc-PYP uptake using the volumetric parameters, cardiac PYP volume (CPV) and cardiac PYP activity (CPA). We also calculated the SUVmax ratios of myocardial SUVmax/blood pool SUVmax, myocardial SUVmax/bone SUVmax, and the SUVmax retention index. We assessed the correlations between uptake parameters and the four functional parameters associated with prognosis, namely left ventricular ejection fraction, global longitudinal strain, myocardial extracellular volume, and troponin T. CPV and CPA correlated more closely than the SUVmax ratios with the four prognostic factors. Significant correlations between volumetric parameters and prognostic factors were equivalent between 1 and 3 hours. CONCLUSIONS: The disease burden of ATTR-CM was quantified more accurately by volumetric evaluation of 99mTc-PYP SPECT/CT than SUVmax ratios and the performance was equivalent between 1 and 3 hours.

Synthesis and evaluation of a deltic guanidinium analogue of a cyclic RGD peptide.

A guanidine group is abundantly found in natural products and drugs. Guanidine has the highest basicity among many common functional groups in nature. Because of its high basicity, it generally exists as a protonated guanidinium and functions as a cationic hydrogen bond donor. Finding an appropriate bioisostere of guanidinium is challenging because of its high basicity and unique trigonal planar shape. In this study, we explored the possibility of "deltic guanidinium" as a bioisostere of guanidinium using a cyclic arginine-glycine-aspartic acid (RGD) peptide as a parent compound. We synthesized c(deltic RGDyK), in which a guanidinium group of an arginine residue in c(RGDyK) is replaced with deltic guanidinium. A target binding assay, biodistribution study, and metabolic stability assay were conducted with c(deltic RGDyK) and its radioiodinated variant. The deltic guanidinium analog peptides exhibited similar biological properties to the parent peptides and improved in vivo stability, indicating that deltic guanidinium could work as a unique bioisostere of guanidinium.

Long-term outcomes and prognostic factors of patients with lung metastases from differentiated thyroid cancer after radioiodine therapy in Japan.

Long-term survival in patients with differentiated thyroid cancer (DTC) and lung metastasis remains unexplored in Japan. This study aimed to investigate the long-term survival and prognostic factors of radioiodine therapy (RIT) in a University Hospital setting. This retrospective study included 62 patients with lung metastases from DTC who received RIT between March 2005 and December 2016. According to the 131I whole-body scan and chest computed tomography results, lung metastases were classified as 131I-avid or non-131I-avid, and miliary, micronodular, or macronodular metastases. The 5- and 10-year overall survival (OS) rates from the initial RIT were calculated by the Kaplan-Meier method, and a proportional hazard fit analysis was performed to determine prognostic factors. With a median follow-up of 7.9 years, the 5- and 10-year OS rates from the initial RIT were 93% and 72%, respectively. Univariable and multivariable analyses of patient subgroups revealed that macronodular lung metastases (defined as nodules >1 cm), older age at initial RIT, and high thyroglobulin values (>400 ng/mL) at initial RIT predicted low OS. The 5- and 10-year OS rates of DTC patients with lung metastases were similar to those in previous Japanese reports, which included a smaller sample size compared with ours. Patients with ≤1 cm lung metastases, aged ≤55 years, and a thyroglobulin level of ≤400 ng/mL at the initial RIT had favorable outcomes.

Phase I/II clinical trial of high-dose [131I] meta-iodobenzylguanidine therapy for high-risk neuroblastoma preceding single myeloablative chemotherapy and haematopoietic stem cell transplantation.

PURPOSE: Paediatric high-risk neuroblastoma has poor prognosis despite modern multimodality therapy. This phase I/II study aimed to determine the safety, dose-limiting toxicity (DLT), and efficacy of high-dose 131I-meta-iodobenzylguanidine (131I-mIBG) therapy combined with single high-dose chemotherapy (HDC) and haematopoietic stem cell transplantation (HSCT) in high-risk neuroblastoma in Japan. METHODS: Patients received 666 MBq/kg of 131I-mIBG and single HDC and HSCT from autologous or allogeneic stem cell sources. The primary endpoint was DLT defined as adverse events associated with 131I-mIBG treatment posing a significant obstacle to subsequent HDC. The secondary endpoints were adverse events/reactions, haematopoietic stem cell engraftment and responses according to the Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) and 123I-mIBG scintigraphy. Response was evaluated after engraftment. RESULTS: We enrolled eight patients with high-risk neuroblastoma (six females; six newly diagnosed and two relapsed high-risk neuroblastoma; median age, 4 years; range, 1-10 years). Although all patients had adverse events/reactions after high-dose 131I-mIBG therapy, we found no DLT. Adverse events and reactions were observed in 100% and 25% patients during single HDC and 100% and 12.5% patients during HSCT, respectively. No Grade 4 complications except myelosuppression occurred during single HDC and HSCT. The response rate according to RECIST 1.1 was observed in 87.5% (7/8) in stable disease and 12.5% (1/8) were not evaluated. Scintigraphic response occurred in 62.5% (5/8) and 37.5% (3/8) patients in complete response and stable disease, respectively. CONCLUSION: 131I-mIBG therapy with 666 MBq/kg followed by single HDC and autologous or allogeneic SCT is safe and efficacious in patients with high-risk neuroblastoma and has no DLT. TRIAL REGISTRATION NUMBER: jRCTs041180030. NAME OF REGISTRY: Feasibility of high-dose iodine-131-meta-iodobenzylguanidine therapy for high-risk neuroblastoma preceding myeloablative chemotherapy and haematopoietic stem cell transplantation (High-dose iodine-131-meta-iodobenzylguanidine therapy for high-risk neuroblastoma). URL OF REGISTRY: https://jrct.niph.go.jp/en-latest-detail/jRCTs041180030 . DATE OF ENROLMENT OF THE FIRST PARTICIPANT TO THE TRIAL: 12/01/2018.

Volumetric evaluation of 99mTc-pyrophosphate SPECT/CT for transthyretin cardiac amyloidosis: Methodology and correlation with cardiac functional parameters.

BACKGROUND: Volumetric evaluation of 99mTechnetium-pyrophosphate (99mTc-PYP) SPECT/CT is a useful method for assessing transthyretin cardiac amyloidosis (ATTR-CA). We investigated the methodology and assessed its relationship with conventional parameters. METHODS AND RESULTS: We retrospectively evaluated 99mTc-PYP SPECT/CT scans of 25 patients who underwent endomyocardial biopsy and/or gene testing. Fourteen (56%) patients were diagnosed with ATTR-CA. SPECT/CT images were acquired at 3 hours after injection. Total volumes of the myocardial regions where uptakes were > 1.2 and 1.4 × aortic blood pool SUVmax were evaluated and defined as cardiac pyrophosphate volume (CPV1.2 and CPV1.4). The heart-to-contralateral lung (H/CL) ratio and myocardial SUVmax were also calculated. CPV1.2 achieved the highest sensitivity and specificity in diagnosing ATTR-CA. In patients diagnosed with ATTR-CA (n = 14), CPV1.2 negatively correlated with left ventricular ejection fraction and positively correlated with left ventricular posterior wall thickness and QRS duration. The correlation was stronger in CPV1.2 than in the H/CL ratio and SUVmax. CONCLUSION: Volumetric evaluation of 99mTc-PYP SPECT/CT may be superior to the H/CL ratio and SUVmax in assessing the disease burden of ATTR-CA. Larger studies are warranted to clarify whether volumetric measurement can assess prognosis and disease progression.

Visualization of Dynamic Expression of Myocardial Sigma-1 Receptor After Myocardial Ischemia and Reperfusion Using Radioiodine-Labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) Imaging.

BACKGROUND: This study chronologically evaluated the expression of the intensity and distribution of the sigma-1 receptor (σ1R) demonstrated by radiolabeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) in a rat model of myocardial ischemia and reperfusion.Methods and Results:The left coronary artery was occluded for 30 min, followed by reperfusion. Dual-tracer autoradiography with 125I-OI5V and 99 mTc-MIBI was performed to assess the spatiotemporal changes in 125I-OI5V uptake (n=5-6). Significant and peaked 125I-OI5V uptake in the ischemic area was observed at 3 days after reperfusion, and the 125I-OI5V uptake ratio of ischemic area to normally perfused left ventricular area decreased gradually from 3 to 28 days (mean value±SD; 0.90±0.12 at 1 day, 1.89±0.19 at 3 days, 1.52±0.17 at 7 days, 1.34±0.13 at 14 days, and 1.16±0.14 at 28 days, respectively). Triple-tracer autoradiography with 125I-OI5V, 99 mTc-MIBI, and 201TlCl was performed to evaluate 125I-OI5V uptake in the ischemic area in relation to the residual perfusion at 7 days (n=4). The 125I-OI5V uptake ratio of the non-salvaged area was higher compared to that of the salvaged area in the ischemic area. 123I-OI5V and 99 mTc-MIBI SPECT/CT was performed 3 days after reperfusion (n=3), and the in vivo images showed clear uptake of 123I-OI5V in the perfusion defect area. CONCLUSIONS: The present study confirmed the spatiotemporal expression pattern of σ1R expression. Non-invasive σ1R imaging with 123I or 125I-OI5V was feasible to monitor the expression of σ1R after myocardial ischemia and reperfusion.

Postconditioning Accelerates Myocardial Inflammatory Resolution Demonstrated by 14C-Methionine Imaging and Attenuates Ventricular Remodeling After Ischemia and Reperfusion.

BACKGROUND: Methionine uptake after myocardial infarction has been proven to reflect myocardial inflammation. The effect of postconditioning on the post-infarction inflammatory process, however, remains to be elucidated.Methods and Results:In control (n=22) and postconditioning rats (n=23), the left coronary artery was occluded for 30 min, followed by reperfusion for 1, 3, 7, and 14 days. Postconditioning was performed immediately following the reperfusion. 14C-methinine (0.74 MBq) and 201Tl (14.8 MBq) were injected 20 and 10 min prior to sacrifice, respectively. One minute before sacrifice, 150-180 MBq of 99 mTc-MIBI was injected immediately following the re-occlusion of the left coronary artery to verify the area at risk, and left ventricular triple-tracer autoradiography was performed. To examine the ventricular remodeling, echocardiography was performed 2 months after reperfusion in both groups (n=6 each). In the control rats, the methionine uptake ratios on days 1, 3, 7, and 14 were 0.74±0.12, 1.85±0.16, 1.48±0.10, 1.25±0.04, respectively. With postconditioning, methionine uptake was similar on day 3 (1.90±0.21), but was lower on day 7 (1.23±0.22, P<0.05) and day 14 (1.08±0.09, P<0.005). Echocardiography revealed that postconditioning reduced the ventricular end-diastolic (0.97±0.16 to 0.78±0.12 cm, P<0.05) and systolic (0.85±0.21 to 0.55±0.23 cm, P<0.05) dimensions and improved ventricular percentage fractional shortening (12±6.2 to 29±12 %, P=0.01). CONCLUSIONS: 14C-methinine imaging revealed that postconditioning accelerated resolution of inflammation and attenuated ventricular remodeling.

[Hyper-IL-6 syndrome mimicking IgG4-related disease].

Distinguishing between IgG4-related disease (IgG4-RD) and hyper-interleukin (IL) -6 syndrome, such as immune mediated conditions, autoimmune diseases, and idiopathic multicentric Castleman disease (iMCD) is challenging. Here, we report the case of a 69-year-old man with cervical lymphadenopathy who was admitted to our hospital and histologically diagnosed with hyper-IL-6 syndrome mimicking IgG4-RD phenotypically. Laboratory data detected polyclonal hypergammaglobulinemia comprising IgG, including IgG4 (2,350 mg/dl). Computed tomography revealed presence of systemic lymphadenopathy, enlarged bilateral submandibular glands, and infiltrative shadow in the right lower lung. Magnetic resonance imaging revealed diffusely enlarged pancreas the size of a sausage and hypointense rim on T2, suggesting autoimmune pancreatitis as part of IgG4-RD. Biopsy of the cervical lymph node revealed proliferation of IL-6-positive mature plasma cells in the expanded interfollicular area with an elevated IgG4+/IgG+ cell ratio (approximately 70%). These histological findings were consistent with hyper-IL-6 syndrome rather than IgG4-RD; however, the serum IL-6 level was slightly elevated. Bone marrow aspiration detected both IgG4- and IL-6-positive mature plasma cells. Although this case cannot be diagnosed as IgG4-RD because it failed to meet its diagnostic criteria, administration of oral prednisolone (0.5 mg/kg) resulted in rapidly improved lymphadenopathy, enlarged pancreas, and serological findings. This report can be helpful for the diagnostic assessment of polyclonal hypergammaglobulinemia conditions.

[Influence of the Each Correction Method for the Specific Binding Ratio and Standardized Uptake Value in the Dopamine Transporter SPECT].

This study was to reveal the characteristics for each correction effect of specific binding ratio (SBR) and standardized uptake value (SUV) in the dopamine transporter (DAT) single photon emission computed tomography (SPECT). We created the 123I solution of five radioactive concentrations, which was filled with two types of striatum phantom such as separated or integrated caudate and putamen. We created 10 striatum accumulation models by combining the 123I solution. Images were reconstructed using ordered subset expectation maximization (OSEM) incorporating attenuation correction (AC), scatter correction (SC) or resolution recovery (RR) for the collected data of 10 striatum accumulation models and 66 patients. Correction combinations were AC, ACSC, ACRR and ACSCRR. The SBR, SUVmean and SUVmax were evaluated correlation and relative error between SBR, SUVmean and SUVmax by each correction method. The SBR and SUV had a significant positive correlation with all correction methods. The minimum values of relative error for SBR, SUVmean and SUVmax were 39.7% with ACSCRR, 18.4% with AC and 16.5% with ACSC, respectively. In addition, the ACSC of SBR and SUVmean was almost same value. The SBR showed significantly higher values by incorporating SC, while the SUV was significantly higher values by incorporating RR. It was suggested that SUV could be used for the quantitative index of DAT SPECT. Furthermore, we demonstrated the characteristic among each correction for SBR and SUV.

A Case of Dermatomyositis with Severe Myalgia and Muscle Weakness Testing Positive for Anti-melanoma Differentiation-associated Gene 5 Antibody.

We report a case of a woman with typical dermatomyositis (DM) with skin manifestations, severe myalgia and muscle weakness complicated by interstitial lung disease (ILD) and pneumomediastinum. Pneumomediastinum persisted despite treatment with immunosuppressive therapy (steroids and cyclosporine). After the test for anti-melanoma differentiation-associated gene 5 (MDA5) antibody came out positive, we doubled the cyclosporine dose and her condition improved. Despite typical clinical features of DM, in cases complicated by pneumomediastinum or steroid resistance, measurement of anti-MDA5 antibody may be useful for immunosuppressant dose titration.

Alternative to Rituximab Therapy for a Patient with Ankylosing Spondylitis Who Was Unable to Continue Anti-TNF Therapy.

We herein present a case of a 38-year-old man who had bamboo spine and severe sacroiliitis and who was diagnosed with ankylosing spondylitis (AS). Infliximab (IFX) markedly improved the axial symptom but was discontinued due to the side effect of peripheral neuropathy. Switching from IFX to etanercept worsened the side effect. Rituximab (RTX) administration elicited a good response without side effects. RTX might be a suitable option for AS therapy when TNF inhibitors are difficult to use.

Triple-phase contrast-enhanced MRI for the prediction of preoperative chemotherapeutic effect in patients with osteosarcoma: comparison with (99m)Tc-MIBI scintigraphy.

OBJECTIVE: This study aims to determine whether (99m)Tc-MIBI scintigraphy and triple-phase contrast-enhanced magnetic resonance imaging (TCE-MRI) performed during and after preoperative chemotherapy have the power to predict final chemotherapeutic effects in patients with osteosarcoma (OS). MATERIALS AND METHODS: Seventeen patients underwent (99m)Tc-MIBI scintigraphy and TCE-MRI before and after the middle and last courses of preoperative chemotherapy. As for (99m)Tc-MIBI scintigraphy, an uptake ratio (UR) and a reduction rate of UR (ΔUR(MIBI)) were calculated. As for TCE-MRI, a ratio of contrast to background (CTB) was calculated in the whole tumor area (WA) at each phase on dynamic T1-weighted fat suppression images. Then a ratio of signal (R(WA)) was calculated by dividing CTB at triple-phase by CTB at pre-phase. RESULTS: Nine and eight patients showed good and poor response in histopathologic evaluation. The sensitivity, specificity, and accuracy for the prediction of histopathological chemotherapeutic effect was 44, 100, 69% in R(WA) at the first phase, 100, 75, 88% in ΔUR(MIBI) after the middle course, 88, 100, 94% in R(WA) at the first phase, and 100, 75, 88% in ΔUR(MIBI) after the last course of the preoperative chemotherapy, respectively. CONCLUSION: Both (99m)Tc-MIBI scintigrapy and TCE-MRI can predict the tumor response in patients with OS after the completion of the preoperative chemotherapy.

Diagnostic Performance of Artificial Neural Network for Detecting Ischemia in Myocardial Perfusion Imaging.

BACKGROUND: The purpose of this study was to apply an artificial neural network (ANN) in patients with coronary artery disease (CAD) and to characterize its diagnostic ability compared with conventional visual and quantitative methods in myocardial perfusion imaging (MPI). METHODS AND RESULTS: A total of 106 patients with CAD were studied with MPI, including multiple vessel disease (49%), history of myocardial infarction (27%) and coronary intervention (30%). The ANN detected abnormal areas with a probability of stress defect and ischemia. The consensus diagnosis based on expert interpretation and coronary stenosis was used as the gold standard. The left ventricular ANN value was higher in the stress-defect group than in the no-defect group (0.92±0.11 vs. 0.25±0.32, P<0.0001) and higher in the ischemia group than in the no-ischemia group (0.70±0.40 vs. 0.004±0.032, P<0.0001). Receiver-operating characteristics curve analysis showed comparable diagnostic accuracy between ANN and the scoring methods (0.971 vs. 0.980 for stress defect, and 0.882 vs. 0.937 for ischemia, both P=NS). The relationship between the ANN and defect scores was non-linear, with the ANN rapidly increased in ranges of summed stress score of 2-7 and summed defect score of 2-4. CONCLUSIONS: Although the diagnostic ability of ANN was similar to that of conventional scoring methods, the ANN could provide a different viewpoint for judging abnormality, and thus is a promising method for evaluating abnormality in MPI.

Multicenter cross-calibration of I-123 metaiodobenzylguanidine heart-to-mediastinum ratios to overcome camera-collimator variations.

BACKGROUND: The heart-to-mediastinum ratio (HMR) of (123)I-metaiodobenzylguanidine (MIBG) showed variations among institutions and needs to be standardized among various scinticamera-collimator combinations. METHODS: A total of 225 phantom experiments were performed in 84 institutions to calculate cross-calibration coefficients of HMR. Based on phantom studies, a conversion coefficient for each camera-collimator system was created, including low-energy (LE, n = 125) and a medium-energy (ME, n = 100) collimators. An average conversion coefficient from the most common ME group was used to calculate the standard HMR. In clinical MIBG studies (n = 52) from three institutions, HMRs were standardized from both LE- and ME-type collimators and classified into risk groups of <1.60, 1.60-2.19, and ≥2.20. RESULTS: The average conversion coefficients from the individual camera-collimator condition to the mathematically calculated reference HMR ranged from 0.55 to 0.75 for LE groups and from 0.83 to 0.95 for ME groups. The conversion coefficient of 0.88 was used to unify HMRs from all acquisition conditions. Using the standardized HMR, clinical studies (n = 52) showed good agreement between LE and ME types regarding three risk groups (κ = 0.83, P < .0001, complete agreement in 90%, 42% of the patients reclassified into the same risk group). CONCLUSION: By using the reference HMR and conversion coefficients for the system, HMRs with various conditions can be converted to the standard HMRs in a range of normal to low HMRs.

Area of ischemia assessed by physicians and software packages from myocardial perfusion scintigrams.

BACKGROUND: The European Society of Cardiology recommends that patients with >10% area of ischemia should receive revascularization. We investigated inter-observer variability for the extent of ischemic defects reported by different physicians and by different software tools, and if inter-observer variability was reduced when the physicians were provided with a computerized suggestion of the defects. METHODS: Twenty-five myocardial perfusion single photon emission computed tomography (SPECT) patients who were regarded as ischemic according to the final report were included. Eleven physicians in nuclear medicine delineated the extent of the ischemic defects. After at least two weeks, they delineated the defects again, and were this time provided a suggestion of the defect delineation by EXINI HeartTM (EXINI). Summed difference scores and ischemic extent values were obtained from four software programs. RESULTS: The median extent values obtained from the 11 physicians varied between 8% and 34%, and between 9% and 16% for the software programs. For all 25 patients, mean extent obtained from EXINI was 17.0% (± standard deviation (SD) 14.6%). Mean extent for physicians was 22.6% (± 15.6%) for the first delineation and 19.1% (± 14.9%) for the evaluation where they were provided computerized suggestion. Intra-class correlation (ICC) increased from 0.56 (95% confidence interval (CI) 0.41-0.72) to 0.81 (95% CI 0.71-0.90) between the first and the second delineation, and SD between physicians were 7.8 (first) and 5.9 (second delineation). CONCLUSIONS: There was large variability in the estimated ischemic defect size obtained both from different physicians and from different software packages. When the physicians were provided with a suggested delineation, the inter-observer variability decreased significantly.