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.

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.

(-)-o-[11 C]methyl-trans-decalinvesamicol ((-)-[11 C]OMDV) as a PET ligand for the vesicular acetylcholine transporter.

To develop a PET imaging agent to visualize brain cholinergic neurons and synaptic changes caused by Alzheimer's disease, (-)- and (+)-o-[11 C]methyl-trans-decalinvesamicol ([11 C]OMDV) were isolated and investigated for differences in not only their binding affinity and selectivity to vesicular acetylcholine transporter (VAChT), but also their in vivo activities. [11 C]OMDV has a high binding affinity for VAChT both in vitro and in vivo. Racemic OMDV and o-trimethylstannyl-trans-decalinvesamicol (OTDV), which are precursors for synthesis of [11 C]OMDV, were separated into (-)-optical isomers ((-)-OMDV and (-)-OTDV) and (+)-optical isomers ((+)-OMDV and (+)-OTDV) by HPLC. In the in vitro binding assay, (-)-OMDV(7.2 nM) showed eight times higher binding affinity (Ki) to VAChT than that of (+)-OMDV(57.5 nM). In the biodistribution study, the blood-brain barrier permeability of both enantiomers ((-)-[11 C]OMDV and (+)-[11 C]OMDV) was similarly high (about 1.0%ID/g) at 2 min post-injection. However, (+)-[11 C]OMDV clearance from the brain was faster than (-)-[11 C]OMDV. In the in vivo blocking study, accumulation of (-)-[11 C]OMDV in the cortex was markedly decreased (approximately 30% of control) by coadministration of vesamicol, and brain uptake of (-)-[11 C]OMDV was not significantly altered by coadministration of (+)-pentazocine or (+)-3-(3-hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP). PET-CT imaging revealed inhibition of the rat brain uptake of (-)-[11 C]OMDV by coadministration of vesamicol. In conclusion, (-)-[11 C]OMDV, which is an enantiomer of OMDV, selectively binds to VAChT with high affinity in the rat brain in vivo. (-)-[11 C]OMDV may be utilized as a potential PET ligand for studying presynaptic cholinergic neurons in the brain.

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.

123I-MIBG myocardial scintigraphy for the diagnosis of DLB: a multicentre 3-year follow-up study.

BACKGROUND AND PURPOSE: We previously reported the usefulness of iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy for differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) in a cross-sectional multicentre study. The aim of this study was, by using reassessed diagnosis after 3-year follow-up, to evaluate the diagnostic accuracy of 123I-MIBG scintigraphy in differentiation of probable DLB from probable AD. METHODS: We undertook 3-year follow-up of 133 patients with probable or possible DLB or probable AD who had undergone 123I-MIBG myocardial scintigraphy at baseline. An independent consensus panel made final diagnosis at 3-year follow-up. Based on the final diagnosis, we re-evaluated the diagnostic accuracy of 123I-MIBG scintigraphy performed at baseline. RESULTS: Sixty-five patients completed 3-year follow-up assessment. The final diagnoses were probable DLB (n=30), possible DLB (n=3) and probably AD (n=31), and depression (n=1). With a receiver operating characteristic curve analysis of heart-to-mediastinum (H/M) ratios for differentiating probable DLB from probable AD, the sensitivity/specificity were 0.77/0.94 for early images using 2.51 as the threshold of early H/M ratio, and 0.77/0.97 for delayed images using 2.20 as the threshold of delayed H/M ratio. Five of six patients who were diagnosed with possible DLB at baseline and with probable DLB at follow-up had low H/M ratio at baseline. CONCLUSIONS: Our follow-up study confirmed high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy at baseline and the clinical diagnosis of probable DLB at 3-year follow-up. Its diagnostic usefulness in early stage of DLB was suggested. TRIAL REGISTRATION NUMBER: UMIN00003419.

Development and validation of a direct-comparison method for cardiac (123)I-metaiodobenzylguanidine washout rates derived from late 3-hour and 4-hour imaging.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Comparison of 18 F-FDG PET Findings of Pegfilgrastim-Induced Aortitis With Other Types of Large-Vessel Vasculitis : A Retrospective Observational Study.

PURPOSE OF THE REPORT: To elucidate the PET/CT findings of pegfilgrastim-induced aortitis (PFIA) and compare them with those of other large-vessel vasculitis. METHODS: We enrolled 45 patients diagnosed with the following: PFIA, n = 8; Takayasu arteritis (TA), n = 12; giant cell arteritis (GCA), n = 6; and immunoglobulin G4-related aortitis (IgG4-A), n = 19. Records of PET/CT performed before treatment initiation were collected. The aorta and its branches were divided into 16 anatomic regions. Presence of abnormal 18 F-FDG uptake in each region was determined and measured. RESULTS: The 18 F-FDG-positive areas of PFIA were distributed in the regions of the ascending aorta to the suprarenal abdominal aorta, cervical branches of the aorta, and external iliac arteries, similar to those of TA. However, TA had a higher proportion of 18 F-FDG-positive areas than PFIA in almost all anatomic regions. These areas of GCA were widespread throughout the entire aorta and the upper and lower limbs, whereas those of IgG4-A were observed from the abdominal aorta to iliac arteries. SUV max , SUV peak , metabolic volume, and total lesion glycolysis were higher in GCA than in PFIA, TA, and IgG4-A. CONCLUSIONS: Pegfilgrastim-induced aortitis distribution on PET/CT was frequently observed in the aorta, cervical branches, and extra iliac arteries. The low proportion of 18 F-FDG-positive areas in PFIA was different from that of TA, GCA, and IgG4-A. These findings may help identify and differentiate various aortitis types in clinical practice.

A Viability Analysis of Tumor-Bearing Frozen Autograft for the Reconstruction After Resection of Malignant Bone Tumors Using 99m Tc-MDP Scintigraphy.

PURPOSE OF THE REPORT: Several methods are used to reconstruct bony defects after malignant tumor excision. Tumor-bearing frozen autograft reconstruction is a biological procedure in which tumor-bearing bone is reused after devitalization with liquid nitrogen to kill tumor cells. The viability of frozen autografts has not been fully evaluated over time. We therefore aimed to evaluate the viability of devitalized bone grafts, using 99m Tc-MDP scintigraphy. PATIENTS AND METHODS: Seventy-four patients who underwent frozen autograft reconstruction after the excision of a malignant bone tumor were enrolled. Two hundred forty-two postoperative 99m Tc-MDP scans were reviewed. For a quantitative analysis, the region of interest on the frozen bone segment and a symmetric region of interest on the contralateral normal area were manually set. The radioactive tracer uptake ratio was calculated by dividing the count density of the frozen bone segment by that of the contralateral normal area in each image. An uptake ratio of 0.9 to 1.1 was defined as a normalization of tracer uptake. RESULTS: Normalization of tracer uptake was achieved in 95% to 97% of the cases by 60 months postoperatively, and earlier in the middle zone and peripheral zone in the pedicle freezing group in comparison to the free freezing group (both P = 0.03). Fracture and nonunion was associated with a low uptake ratio, whereas infection was associated with a high uptake ratio before the occurrence of the event. CONCLUSIONS: The calculation of the uptake ratio using 99m Tc-MDP scans was an objective and accurate evaluation method. The period to normalization of tracer uptake in the pedicle frozen bone was significantly earlier than that in the free frozen bone. The postoperative complications can be also predicted.

Standardization of metaiodobenzylguanidine heart to mediastinum ratio using a calibration phantom: effects of correction on normal databases and a multicentre study.

PURPOSE: This study was performed to demonstrate that the results obtained with a calibration phantom could be used as a tool for standardizing measurement of heart to mediastinum (H/M) ratio in cardiac metaiodobenzylguanidine (MIBG) imaging. METHODS: Images of the phantom containing (123)I-MIBG were acquired on the cameras in 10 hospitals (11 camera types) to determine the relationship between H/M ratios using different collimators: low-energy (LE) and medium-energy (ME)/low-medium-energy (LME) collimators. The effect of standardization on the ME-comparable H/M ratio was examined in two settings: a Japanese standard MIBG database (n = 62) and multicentre studies (n = 49). In a multicentre study, probable Alzheimer's disease (AD, n = 18) and probable dementia with Lewy bodies (DLB, n = 31) were studied and standardized by the calibration phantom method. RESULTS: Linear regression equations between LE and ME collimators were obtained for the phantom study in all institutions. When the H/M ratio with an LE collimator was corrected based upon the calibration phantom, the corrected values were comparable to those obtained using ME collimators. The standard database also exhibited a normal distribution after standardization as determined by skewness and goodness-of-fit test. A mixture of the populations by LE and ME collimators showed significant separation of AD and DLB groups (F ratio = 24.9 for the late H/M), but the corrected values resulted in higher F ratios for both early and late H/M (F ratio = 34.9 for the late H/M). CONCLUSION: Standardization of H/M ratios by the heart-chest calibration phantom method is feasible among different collimator types. This method could be practically used for multicentre comparison of H/M ratios.

A novel combined radiological method for evaluation of the response to chemotherapy for primary bone sarcoma.

BACKGROUND: In the treatment of bone sarcoma, evaluation of chemotherapeutic effects is extremely important. In this study, we compared radiological evaluations and histological response, and developed a combined radiological scoring system for assessing the response to chemotherapy. METHODS: A total of 79 patients with primary bone sarcomas were examined by X-ray photography (Xp), angiography, MRI, 201Tl scintigraphy (Tl) and 99mTc-MIBI scintigraphy (MIBI) to evaluate their response to preoperative chemotherapy. Patients were classified as responders and non-responders according to radiological images. All resected tumors were evaluated histologically and classified as a good response (≥90% necrosis) or a poor response (≤90% necrosis). The sensitivity, specificity, accuracy, and kappa values in radiological evaluation were calculated. Furthermore, we developed a combined radiological scoring system that correlated the results of radiological images with histological response. RESULTS: Sensitivity, specificity, and accuracy were 90.9%, 38.2%, and 67.5% (K = 0.31), respectively, for Xp; 91.7%, 33.3%, and 66.7% (K = 0.27) for angiography; 81.0%, 67.6%, and 75.0% (K = 0.49) for MRI; 78.9%, 72.4%, and 76.1% (K = 0.51) for Tl; 85.3%, 69.2%, and 78.3% (K = 0.55) for MIBI; and 93.3%, 76.5%, and 86.1% (K = 0.71) for combined radiological scoring. CONCLUSIONS: Combined radiological evaluations showed high correlation with histological response for assessing the effects of chemotherapy.

Assessment of doxorubicin cardiac toxicity using gated 99mTc-hexakis-2-methoxyisobutylisonitrile myocardial single photon emission computed tomography: wall thickening and motion abnormalities can be an early sign of cardiac involvement.

BACKGROUND: Advancement in chemotherapy has significantly improved the prognosis of cancer patients. However, many anticancer drugs have serious cardiovascular side effects. We assessed doxorubicin-induced cardiac toxicity (DCT) during and after preoperative chemotherapy using gated (99m)Tc-hexakis-2-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) in patients with malignant bone and soft tissue tumors. METHODS AND RESULTS: Gated (99m)Tc-MIBI SPECT was performed before, and after the middle and final courses of preoperative chemotherapy. Gated (99m)Tc-MIBI SPECT was quantitatively analyzed with QGS/QPS software. We also assessed the reproducibility of measurements of global and regional functions from gated SPECT images. Twenty-eight patients (19 males and 9 females), eligible for preoperative chemotherapy, were included. All patients had normal myocardial perfusion images based on QPS during preoperative chemotherapy. Wall thickening (WT) and motion (WM) decreased after the middle course of preoperative chemotherapy compared to baseline. After the final course of preoperative chemotherapy, significant decreases of ejection fraction, WT and WM, and one-third mean filling rate were observed compared to baseline. By regression analysis, correlation coefficients of inter- and intra-observer reproducibility of global and regional functions were excellent (r ≥ 0.95). CONCLUSIONS: Gated (99m)Tc-MIBI SPECT can monitor the deterioration of cardiac function in asymptomatic patients with possible DCT. WT and WM might be useful as early markers of ventricular dysfunction due to DCT.

Feasibility of 125I-RGD uptake as a marker of angiogenesis after myocardial infarction.

OBJECTIVE: Angiogenesis is an important process facilitating the healing process after myocardial infarction. 125I-RGD imaging may be a promising candidate to image angiogenesis but may also detect inflammation. METHODS: Left coronary artery was occluded for 30 min, followed by reperfusion in a rat model (n = 31). One, 3, 7 and 14 days, 1 and 2 months later, Triple-tracer autoradiography was performed. 125I-RGD (1.5 MBq) and 201Tl (15 MBq) were injected at 80 and 10 min before sacrifice. Left coronary artery was reoccluded and 99mTc-MIBI (150-180 MBq) was injected 1 min before sacrifice to verify the area at risk. Angiogenesis and macrophage infiltration were evaluated by immunohistochemical analysis with anti-alpha-smooth muscle actin and anti-CD68, respectively. RESULTS: 125I-RGD uptake ratio in the area at risk was weak at day 3 (1.23 ± 0.23 but increased markedly and peaked at day 7 (2.27 ± 0.37) followed by a gradual reduction until 1 and 2 months later (1.93 ± 0.16 at 1 month, 1.58 ± 0.15 at 2 month). In the immunohistochemical analysis, copious staining of anti-CD68 cells was observed, with anti-SMA cells stained only minimally at day 3. The number of anti-CD68 cells was decreased significantly at day 7 but largely absent at 1 month. Anti-SMA positive cells peaked at day 7 and reduced gradually until 1 month. CONCLUSIONS: Myocardial 125I-RGD uptake reflects angiogenesis rather than inflammation after myocardial infarction.

Development of Radiohalogenated Osimertinib Derivatives as Imaging Probes for Companion Diagnostics of Osimertinib.

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for treating non-small-cell lung cancer (NSCLC) with EGFR mutations. Genetic testing is required to detect the mutation for selecting patients who can use osimertinib. Here, we report an attempt to develop nuclear imaging probes that detect the EGFR mutations. We designed and synthesized I-osimertinib and Br-osimertinib with a radioactive or nonradioactive halogen atom at an indole ring in osimertinib and evaluated them. In vitro assays suggested that both I-osimertinib and Br-osimertinib exhibit a specifically high activity toward NSCLC with EGFR L858R/T790M mutations. In biodistribution experiments, the accumulation of both [125I]I-osimertinib and [77Br]Br-osimertinib in tumors with mutations was significantly higher than that in blood and muscle. However, these osimertinib derivatives showed a significantly higher accumulation in lungs than in tumors. Therefore, for detecting the mutations in lung cancer, further structural modifications of the probes are required.

Use of 99mTc-MIBI scintigraphy in the evaluation of the response to chemotherapy for osteosarcoma: comparison with 201Tl scintigraphy and angiography.

BACKGROUND: In the treatment of osteosarcoma, the chemotherapeutic effect influences decisions regarding the surgical margin, continuation of chemotherapy, and choice of anticancer drugs for further chemotherapy. Therefore, it is necessary to evaluate the response to chemotherapy in the middle of the chemotherapy course. In this study, we investigated the use of (99m)Tc-hexakis-2-methoxyisobutyl-isonitrile ((99m)Tc-MIBI) scintigraphy in evaluating the response to chemotherapy of patients with osteosarcoma in comparison with (201)Tl scintigraphy and angiography. METHODS: A total 45 patients with osteosarcoma were examined using (99m)Tc-MIBI scintigraphy, (201)Tl scintigraphy, and angiography to evaluate their response to chemotherapy. The percentage reduction in the uptake ratios (ΔUR) calculated as 100 × [(prechemotherapy value - postchemotherapy value)/prechemotherapy value] were compared with histological assessments. Similarly, changes in tumor vascularity assessed by angiograms were compared with histological assessments. On the angiographic findings, the results were classified as complete response (CR), partial response (PR), no change (NC), or progressive disease (PD). On the images, ΔUR in (99m)Tc-MIBI ≥ 30% and ΔUR in (201)Tl ≥ 30% were classified as responder, as were CR and PR in angiograms. The therapeutic effect was assessed by histopathological examination of the resected specimens. The tumors of poor responders showed less than 90% necrosis, whereas the tumors of good responders showed 90% or more necrosis. RESULTS: Sensitivity, specificity, and accuracy were 73.9, 84.2, and 78.6%, respectively, for (99m)Tc-MIBI (κ = 0.57); 80.0, 61.1, and 72.1%, respectively, for (201)Tl (κ = 0.42); and 91.7, 35.0, and 65.9%, respectively for angiography (κ = 0.28). CONCLUSION: (99m)Tc-MIBI could be effectively used to predict the final response to chemotherapy of osteosarcoma.

In vitro and in vivo evaluation of [125/123I]-2-[4-(2-iodophenyl)piperidino]cyclopentanol([125/123I]-OI5V) as a potential sigma-1 receptor ligand for SPECT.

INTRODUCTION: We investigated the characteristics of radio-iodinated 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) as a single photon emission computed tomography (SPECT) ligand for mapping sigma-1 receptor (σ-1R), which plays an important role in stress remission in many organs. METHODS: OI5V was synthesized from o-bromobenzaldehyde in three steps. OI5V was evaluated for its affinity to VAChT, σ-1 and σ-2 receptor by in vitro competitive binding assays using rat tissues and radioligands, [3H]vesamicol, ( +)-[3H]pentazocine and [3H]DTG, respectively. [125/123I]OI5V was prepared from o-trimethylstannyl-cyclopentanevesamicol (OT5V) by the iododestannylation reaction under no-carrier-added conditions. In vivo biodistribution study of [125I]OI5V in blood, brain regions and major organs of rats was performed at 2, 10, 30 and 60 min post-injection. In vivo blocking study and ex vivo autoradiography were performed to assess the binding selectivity of [125I]OI5V for σ-1 receptor. SPECT-CT imaging study was performed using [123I]OI5V. RESULTS: OI5V demonstrated high selective binding affinity for σ-1R in vitro. In the biodistribution study, the blood-brain barrier (BBB) permeability of [125I]OI5V was high and the accumulation of [125I]OI5V in the rat cortex at 2 min post-injection exceeded 2.00%ID/g. In the in vivo blocking study, the accumulation of [125I]OI5V in the brain was significantly blocked by co-administration of 0.5 µmol of SA4503 and 1.0 µmol of pentazocine. Ex vivo autoradiography revealed that the regional brain accumulation of [125I]OI5V was similar to σ-1R-rich regions of the rat brain. SPECT images of [123I]OI5V in the rat brain reflected the distribution of sigma receptors in the brain. CONCLUSIONS: This study confirmed that [125/123I]OI5V selectively binds σ-1R in the rat brain in vivo. [123I]OI5V was suggested to be useful as a σ-1R ligand for SPECT.

Colchicine treatment early after infarction attenuates myocardial inflammatory response demonstrated by 14C-methionine imaging and subsequent ventricular remodeling by quantitative gated SPECT.

OBJECTIVE: Colchicine has been used as an anti-inflammatory agent and may be cardioprotective after acute myocardial infarction (AMI). We investigated how colchicine administration after AMI affects the myocardial inflammatory response using 14C-methionine and subsequent ventricular remodeling using single-photon emission computed tomography (SPECT) in a rat model of AMI. METHODS: The left coronary artery (LCA) was occluded for 30 min followed by reperfusion. 14C-methionine was injected at 20 min before sacrifice. The LCA was re-occluded at 1 min before sacrifice and 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) was injected. Colchicine was administered intraperitoneally from day 1 to the day before 14C-methionine injection. Dual-tracer autoradiography of the left ventricular short-axis slices was performed. The methionine uptake ratio in an ischemic area was calculated. 99mTc-MIBI gated SPECT assessed end-diastolic volume (EDV), end-systolic volume (ESV) and left ventricular ejection fraction (LVEF). On Cluster of Differentiation 68 with 4',6-diamidino-2-phenylindole (CD68/DAPI) staining the positive myocardial cell percentage in an ischemic area was calculated. RESULTS: In control rats, 14C-methionine uptake ratios on day 3 and 7 were 1.87 ± 0.15 and 1.39 ± 0.12, respectively. With colchicine, the uptake was reduced on days 3 (1.56 ± 0.26, p = 0.042) and 7 (1.23 ± 0.10, p = 0.030). Colchicine treated rats showed smaller EDV, ESV, and higher LVEF compared with control rats. At 8 weeks, those in control rats were 864 ± 115 µL, 620 ± 100 µL, 28.4 ± 2.5%, and in colchicine rats 665 ± 75 µL, 390 ± 97 µL, 42.2 ± 8.5% (p = 0.012, 0.0061, 0.0083), respectively. In control rats, CD68/DAPI positive myocardial cell percentages on days 3 and 7 were 38.4 ± 1.9% and 24.0 ± 2.4%, respectively. With colchicine, the percentages were reduced significantly on both days 3 (31.5 ± 2.0%, p < 0.0001) and 7 (12.0 ± 1.6%, p < 0.0001) as compared with the control. CONCLUSIONS: Short-term colchicine treatment after AMI attenuated the post-AMI inflammatory response and subsequent ventricular remodeling and dysfunction. 14C-methionine imaging and gated 99mTc-MIBI SPECT would be feasible to monitor the effectiveness of anti-inflammatory therapy and left ventricular function.

Synthesis and evaluation of radiogallium-labeled long-chain fatty acid derivatives as myocardial metabolic imaging agents.

Since long-chain fatty acids work as the primary energy source for the myocardium, radiolabeled long-chain fatty acids play an important role as imaging agents to diagnose metabolic heart dysfunction and heart diseases. With the aim of developing radiogallium-labeled fatty acids, herein four fatty acid-based tracers, [67Ga]Ga-HBED-CC-PDA, [67Ga]Ga-HBED-CC-MHDA, [67Ga]Ga-DOTA-PDA, and [67Ga]Ga-DOTA-MHDA, which are [67Ga]Ga-HBED-CC and [67Ga]Ga-DOTA conjugated with pentadecanoic acid (PDA) and 3-methylhexadecanoic acid (MHDA), were synthesized, and their potential for myocardial metabolic imaging was evaluated. Those tracers were found to be chemically stable in 0.1 M phosphate buffered saline. Initial [67Ga]Ga-HBED-CC-PDA, [67Ga]Ga-HBED-CC-MHDA, [67Ga]Ga-DOTA-PDA, and [67Ga]Ga-DOTA-MHDA uptakes in the heart at 0.5 min postinjection were 5.01 ± 0.30%ID/g, 5.74 ± 1.02%ID/g, 5.67 ± 0.22%ID/g, and 5.29 ± 0.10%ID/g, respectively. These values were significantly lower than that of [123I]BMIPP (21.36 ± 2.73%ID/g). For their clinical application as myocardial metabolic imaging agents, further structural modifications are required to increase their uptake in the heart.

Comparison of Myocardial Ischemia Detection Between Semiconductor and Conventional Anger-type Three-detector SPECT.

Objective: Although semiconductor single-photon emission computed tomography (D-SPECT) has been used for myocardial perfusion imaging, few studies have compared its ability to detect myocardial ischemia with that of 3-detector SPECT (GCA9300R). This study used invasive coronary angiography to determine whether the detectability of myocardial ischemia differs between D-SPECT and GCA9300R. Materials and methods: This study included 24 patients who were assessed by coronary angiography within 60 days of myocardial perfusion D-SPECT and GCA9300R. Two nuclear medicine physicians interpreted myocardial perfusion D-SPECT and GCA9300R images with five grades of confidence, then defined regions of ischemia on polar maps. The gold standard was determined by another nuclear cardiology specialist based on integrated assessment of the coronary angiography findings and other clinical information derived from medical charts. The concordance rate and the Cohen kappa (κ) between D-SPECT and GCA9300R were calculated. Results: The sensitivity, specificity, negative and positive predictive values, and the accuracy of patient-based diagnoses were 66.7%, 91.7%, 89.2%, 72.8%, and 85.5%, respectively, for GCA9300R, and 83.3%, 83.3%, 93.7%, 62.4%, and 83.3%, respectively, for D-SPECT. Interpretations of ischemia did not uncover any significant differences between D-SPECT and GCA9300R. The Cohen κ values of D-SPECT and GCA9300 agreed substantially, moderately and marginally for the left circumflex coronary artery (LCX) (0.68), right coronary artery (RCA) (0.43), and left anterior descending coronary artery (LAD) (0.39), respectively. Conclusions: The detectability of myocardial ischemia is comparable between D-SPECT and GCA9300R. Sensitivity is better for D-SPECT than GCA9300R. However, false-positive D-SPECT findings, especially in the apex and inferior wall should be interpreted with caution.

A Radiological Scoring System for Differentiation between Enchondroma and Chondrosarcoma.

BACKGROUND: It is challenging to differentiate between enchondromas and atypical cartilaginous tumors (ACTs)/chondrosarcomas. In this study, correlations between radiological findings and final diagnosis were investigated in patients with central cartilaginous tumors. METHODS: To evaluate the diagnostic usefulness of radiological findings, correlations between various radiological findings and final diagnoses were investigated in a cohort of 81 patients. Furthermore, a new radiological scoring system was developed by combining radiological findings. RESULTS: Periosteal reaction on X-ray (p = 0.025), endosteal scalloping (p = 0.010) and cortical defect (p = 0.002) on CT, extraskeletal mass (p < 0.001), multilobular lesion (p < 0.001), abnormal signal in adjacent tissue (p = 0.004) on MRI, and increased uptake in bone scan (p = 0.002) and thallium scan (p = 0.027) was significantly correlated with final diagnoses. Based on the correlations between each radiological finding and postoperative histological diagnosis, a radiological scoring system combining these findings was developed. In another cohort of 17 patients, the sensitivity, specificity, and accuracy of the radiological score rates for differentiation between enchondromas and ACTs/chondrosarcomas were 88%, 89%, and 88%, respectively (p = 0.003). CONCLUSION: Radiological assessment with combined radiological findings is recommended to differentiate between enchondromas and ACT/chondrosarcomas.