Upfront F18-choline PET/CT versus Tc99m-sestaMIBI SPECT/CT guided surgery in primary hyperparathyroidism: the randomized phase III diagnostic trial APACH2.

BACKGROUND: The common endocrine disorder primary hyperparathyroidism (PHPT) can be cured by surgery. Preoperative localization of parathyroid adenoma (PTA) by imaging is a prerequisite for outpatient minimally invasive parathyroidectomy (MIP). Compared to inpatient bilateral cervical exploration (BCE) which is performed if imaging is inconclusive, MIP is superior in terms of cure and complication rates and less costly. The imaging procedure F18-choline (FCH) PET/CT outperforms Tc99m-sestaMIBI (MIBI) SPECT/CT for PTA localization, but it is much costlier. The aim of this study is to identify the most efficient first-line imaging modality for optimal patient care in PHPT without added cost to society. METHODS: We will conduct a multicenter open diagnostic intervention randomized phase III trial comparing two diagnostic strategies in patients with PHPT: upfront FCH PET/CT versus MIBI SPECT/CT. The primary endpoint is the proportion of patients in whom the first-line imaging method results in successful MIP and cure. Follow-up including biological tests will be performed 1 and 6 months after surgery. The main secondary endpoint is the social cost of both strategies. Other secondary endpoints are as follows: FCH PET/CT and MIBI SPECT/CT diagnostic performance, performance of surgical procedure and complication rate, FCH PET/CT inter- and intra-observer variability and optimization of FCH PET/CT procedure. Fifty-eight patients will be enrolled and randomized 1:1. DISCUSSION: FCH PET/CT is a highly efficient but expensive imaging test for preoperative PTA localization and costs three to four times more than MIBI SPECT/CT. Whether FCH PET/CT improves patient outcomes compared to the reference standard MIBI SPECT/CT is unknown. To justify its added cost, FCH PET/CT-guided parathyroid surgery should lead to improved patient management, resulting in higher cure rates and fewer BCEs and surgical complications. In the previous phase II APACH1 study, we showed that second-line FCH PET/CT led to a cure in 88% of patients with negative or inconclusive MIBI SPECT/CT. BCE could be avoided in 75% of patients and surgical complication rates were low. We therefore hypothesize that upfront FCH PET/CT would improve patient care in PHPT and that the reduction in clinical costs would offset the increase in imaging costs. TRIAL REGISTRATION: NCT04040946 , registered August 1, 2019.  Protocol version Version 2.1 dated from 2020/04/23.

Itraconazole synergistically increases therapeutic effect of paclitaxel and 99mTc-MIBI accumulation, as a probe of P-gp activity, in HT-29 tumor-bearing nude mice.

P-glycoprotein (P-gp), is an important efflux pump involved in chemotherapy resistance in human colon cancer. We investigated the efficacy of itraconazole as a P-gp inhibitor and its therapeutic synergistic relationship to paclitaxel through 99mTc-MIBI accumulation in HT-29 tumor-bearing nude mice. Histopathological screening along with in vitro experiments was done for further assessment. Itraconazole successfully inhibited P-gp mediated 99mTc-MIBI efflux, increasing its in vitro accumulation in itraconazole-receiving dishes. Notably, the co-administration of itraconazole with paclitaxel significantly enhanced the in vitro cytotoxicity effect of paclitaxel in itraconazole + paclitaxel wells containing HT-29 cells. Compared to the control, tumor volume in mice treated with itraconazole, paclitaxel and itraconazole +paclitaxel showed growth suppression approximately by 36.21, 60.02, and 73.3% respectively. And compared to paclitaxel group, the nude mice co-treated with paclitaxel and itraconazole showed suppression of tumor growth by about 33.31 % at the end of the treatment period. Also the biodistribution result showed that the co-administration of itraconazole with paclitaxel raised the mean tumor radioactivity accumulation compared to control and paclitaxel group. When given paclitaxel alone, the ID% of hepatic and cardiac tissue was reduced while co-administration of itraconazole with paclitaxel increased 99mTc-MIBI accumulation in these organs. Furthermore, the histopathological findings confirmed the biodistribution results. These results demonstrate that although monotherapy with itraconazole or paclitaxel has anti-tumor activity against HT-29 human colorectal cancer, a synergistic anti-tumor activity can be achieved when itraconazole is co-administered with paclitaxel. Also, 99mTc-MIBI is an effective radiotracer for monitoring response to treatment in MDR tumors.

Comparison of 99mTc-MIBI scintigraphy, ultrasound, and mammography for the diagnosis of BI-RADS 4 category lesions.

BACKGROUND: We sought to determine the diagnostic efficacy of Breast-specific gamma imaging (BSGI) in Chinese women with BI-RADS 4 category lesions and to compare this efficacy to that of ultrasound/mammography. METHODS: We retrospectively analyzed data from 177 women that had undergone BSGI of BI-RADS 4 category lesions originally detected via ultrasound and/or mammography. RESULTS: Of these 177 cases, 117 (66.1%) were malignant lesions and 60 (33.9%) were benign. The sensitivity, specificity, positive predictive values, and negative predictive values of BSGI were 94.9% (111/117), 78.3% (47/60), 89.5% (111/124), and 88.7% (47/53), respectively. The specificity and positive predictive values for mammography were 48.3% (29/60) and 77.5% (107/138), while for ultrasound they were 53.3% (32/60) and 79.6% (109/137), respectively. The sensitivity and specificity of BSGI for the detection of lesions ≤1 cm in size were 90.9% (10/11) and 88.0% (22/25), respectively, while for breast lesions >1 cm in size these values were 94.3% (100/106) and 71.4% (25/35), respectively. In addition, BSGI sensitivity and specificity values for dense breast tissue were 94.0% (79/84) and 78.0% (39/50), respectively, whereas for non-dense breast tissue these vales were 97.0% (32/33) and 80.0% (8/10), respectively. The sensitivity of BSGI for invasive ductal carcinomas (IDC) and ductal carcinomas in situ (DCIS) was 98.9% (95/96) and 75.0% (9/12), respectively. The tumor to normal tissue ratio of BSGI for malignant lesions was significantly higher than for benign lesions (2.18 ± 1.17 vs 1.66 ± 0.40, t = 7.56, P<0.05). CONCLUSIONS: These results indicate that BSGI is highly sensitive for the detection of such lesions, achieving good positive/negative predictive values. This suggests that for IDC in particular, BSGI is superior to ultrasound and mammography for the diagnosis of BI-RADS 4 category lesions, although this was less apparent for the diagnosis of DCIS lesions. BSGI exhibited excellent performance in dense breast tissue and for the detection of lesions ≤1 cm in size.

Relationship between the infarct localization and left ventricular rotation parameters following acute ST-segment elevation myocardial infarction.

OBJECTIVE: This study was an investigation of the role of left ventricular (LV) apical rotation seen in the early period after myocardial infarction (MI) in predicting infarct localization. METHODS: A total of 124 patients with a ST-Segment elevation myocardial infarction (STEMI) diagnosis who underwent primary percutaneous coronary intervention (PCI) and 50 healthy volunteers with similar demographic characteristics were included in the study. The relationship between 2-dimenstional speckle tracking echocardiography (STE)-guided LV apical rotation angle measurements and technetium-99m sestamibi-single-photon emission computed tomography (SPECT)-guided infarct localization was evaluated. Conventional echocardiography and STE were performed on average 2 days after PCI, and gated SPECT myocardial perfusion imaging (MPI) was performed within an average of 60 days. RESULTS: The apical rotation angle was lower in patients with an anterior MI compared with those who had an inferior MI and the control group (AntMI-InfMI: 6.51±2.4°, AntMI-Control: 13.20±2.5°, InfMI-Control: 14.3±2.1°; p value: 0.00, 0.00, 0.15, respectively). SPECT MPI analysis revealed the presence of an LV apical scar in all patients with acute anterior MI, but only 14 of those with inferior MI group (usually the inferoapical wall). The apical rotation angle recorded in patients with apical scar was lower than that of the patients without apical scar (7.6±2.8° and 14.5±2°, respectively; p=0.00). Receiver operating characteristic curve analysis yielded an area under the curve for apical rotation of 0.799 (p<0.01). The optimal cutoff value of 12.1° had a sensitivity of 78.3% and a specificity of 68.2% for predicting LV apical scar following STEMI. CONCLUSION: Detection of apical rotation angle decrease in the early period after STEMI may be useful in predicting extension of infarct scarring to the LV apex.

99mTc-MIBI uptake as a marker of mitochondrial membrane potential in cancer cells and effects of MDR1 and verapamil.

We investigated the relation of 99mTc-MIBI uptake to mitochondrial membrane potential (MMP) in cancer cell lines and patient-derived tumor cells (PDCs). In T47D and HT29 cells with low MDR1 expression, FCCP dose-dependently reduced MMP and 99mTc-MIBI accumulation in similar patterns with nearly perfect linear relationships. T47D and HT29 cells with high MDR1 expression had low 99mTc-MIBI accumulation that was minimally affected by FCCP dose. In these cells, verapamil markedly increased 99mTc-MIBI accumulation to magnitudes that were excessive compared to MMP increase. Decreased plasma membrane potential by verapamil and its recovery by FCCP suggested that enhanced 99mTc-MIBI transport through modified plasma membranes contributed to the excess accumulation. Evaluation of three different colon cancer PDCs with low to modest MDR1 expression verified that FCCP significantly suppressed MMP and similarly reduced 99mTc-MIBI accumulation. Verapamil partially recovered both MMP and 99mTc-MIBI accumulation that was lowered by FCCP. Importantly, a high linear correlation was found (r = 0.865) between 99mTc-MIBI accumulation and MMP in these cells. These findings indicate that low baseline 99mTc-MIBI uptake that is markedly increased by verapamil represents cancer cells with high levels of MDR1 expression. However, in cancer cells with low or modest levels of MDR1 expression that do not markedly increase 99mTc-MIBI uptake by verapamil, the magnitude of uptake is largely dependent on cellular MMP.

Interobserver Agreement of Planar and SPECT Tc99m-MIBI Scintigraphy for the Assessment of Hypofunctioning Thyroid Nodules.

INTRODUCTION: Thyroid scintigraphy with 99mTc-methoxyisobutylisonitrile (MIBI) is a helpful tool for the risk stratification of thyroid nodules (TN). Whereas a nodule with low or hypointense MIBI uptake has a low risk for malignancy, a hyperintense uptake may indicate a malignant nodule, which requires surgical resection. The appropriate diagnostic or therapeutic regimen of an isointense nodule with an uptake similar to the paranodular tissue is discussed controversially. Aim of this study was to assess the interobserver agreement (IA) for the assignment of TN to the three categories: hypo-, iso-or hyperintense. METHODS: Retrospective analysis of planar and SPECT images of MIBI scintigraphy was performed in 36 randomly selected patients with hypofunctioning TN and histological diagnosis. Four observers with different levels of experience in MIBI-scintigraphy analyzed MIBI uptake and assigned the nodules to the appropriate category. To assess the IA, Fleiss' Kappa was calculated. RESULTS: The study cohort included 11 patients with papillary thyroid carcinoma (diameter 20.3 mm) and 25 patients with benign nodules (diameter 24.8 mm). The IA for all nodules using planar images was 0.76 compared to 0.80 for SPECT images. The IA was better in the subgroup of malignant nodules for planar images as well as SPECT images (Kappa 0.91 and 0.90, respectively) compared to benign nodules (0.65 and 0.76, respectively). Using SPECT images, only one thyroid carcinoma presented with hypointense uptake, the remainder with hyper- or isointense uptake. In contrast, benign nodules were found in all categories. CONCLUSION: MIBI scintigraphy shows a good IA for the interpretation of thyroid carcinoma. The IA is further improved if MIBI scintigraphy is performed in SPECT technique.

Quantitative analysis of technetium-99m-sestamibi uptake and washout in parathyroid scintigraphy supports dual mechanisms of lesion conspicuity.

PURPOSE: Proposed mechanisms of parathyroid localization in 'dual-phase' technetium-99m-sestamibi imaging include increased presence of mitochondria leading to greater uptake and slower washout compared with thyroid tissues owing to reduced expression of P-glycoprotein. Using new techniques of quantitative single-photon emission computed tomography (SPECT)/computed tomography (CT), we have measured MIBI uptake and washout to better understand factors related to conspicuity. PATIENTS AND METHODS: We retrospectively reviewed 125 consecutive patients. Early and delayed SPECT/CT images were reconstructed using a previously validated technique. Maximum standardized uptake values of parathyroid adenomas and thyroid tissue were measured, and corresponding washout rates were calculated. RESULTS: Of 53 patients with localization of parathyroid adenoma (42%), median maximum standardized uptake values were higher for parathyroid adenomas than for thyroid tissue on both early (6.43±3.78 vs. 4.43±1.93, P<0.001) and delayed (3.40±3.09 vs. 1.84±1.05, P<0.001) images, being true on a per-patient basis in 41 (77%) and 48 (91%) patients, respectively. Median washout rates were slower from parathyroid adenomas than from thyroid lobes (0.26±0.16 vs. 0.42±0.18 h, P<0.001), being true on a per-patient basis in 43 (81%) patients. Similar findings were observed in a subgroup of 37 patients with surgically-confirmed adenomas. Of the patients where initial parathyroid uptake did not exceed thyroid uptake, all 12 exhibited slower MIBI washout from the parathyroid adenomas than from the thyroid gland. The characteristics of the thyroid gland did not differ in 67 patients without parathyroid localization. CONCLUSION: Quantitative analysis of 53 patients with localization of parathyroid adenoma revealed both a generally higher initial absolute uptake and slower rate of washout of MIBI in parathyroid adenomas than in thyroid tissue. The findings may support the hypothesis that both mechanisms proposed for parathyroid conspicuity in the dual-phase examination increased mitochondrial binding and slower washout owing to reduced P-glycoprotein expression. The technique of quantitative SPECT/CT represents a powerful tool for measuring tissue uptake to elucidate the contribution of these factors to lesion conspicuity.

Detection of anthracycline-induced cardiotoxicity using perfusion-corrected 99mTc sestamibi SPECT.

By the time cardiotoxicity-associated cardiac dysfunction is detectable by echocardiography it is often beyond meaningful intervention. 99mTc-sestamibi is used clinically to image cardiac perfusion by single photon emission computed tomography (SPECT) imaging, but as a lipophilic cation its distribution is also governed by mitochondrial membrane potential (ΔΨm). Correcting scans for variations in perfusion (using a ΔΨm-independent perfusion tracer such as (bis(N-ethoxy-N-ethyldithiocarbamato)nitrido 99mTc(V)) (99mTc-NOET) could allow 99mTc-sestamibi to be repurposed to specifically report on ΔΨm as a readout of evolving cardiotoxicity. Isolated rat hearts were perfused within a γ-detection apparatus to characterize the pharmacokinetics of 99mTc-sestamibi and 99mTc-NOET in response to mitochondrial perturbation by hypoxia, ionophore (CCCP) or doxorubicin. All interventions induced 99mTc-sestamibi washout; hypoxia from 24.9 ± 2.6% ID to 0.4 ± 6.2%, CCCP from 22.8 ± 2.5% ID to -3.5 ± 3.1%, and doxorubicin from 23.0 ± 2.2% ID to 17.8 ± 0.7, p < 0.05. Cardiac 99mTc-NOET retention (34.0 ± 8.0% ID) was unaffected in all cases. Translating to an in vivo rat model, 2 weeks after bolus doxorubicin injection, there was a dose-dependent loss of cardiac 99mTc-sestamibi retention (from 2.3 ± 0.3 to 0.9 ± 0.2 ID/g with 10 mg/kg (p < 0.05)), while 99mTc-NOET retention (0.93 ± 0.16 ID/g) was unaffected. 99mTc-NOET therefore traps in myocardium independently of the mitochondrial perturbations that induce 99mTc-sestamibi washout, demonstrating proof-of-concept for an imaging approach to detect evolving cardiotoxicity.

99mTc-MIBI Uptake in a Benign Thymic Cyst.

A 34-year-old man with end-stage renal failure status post rejection of a deceased donor kidney transplant presented with bone pain in the setting of elevated serum parathyroid hormone and calcium levels. A Tc-MIBI SPECT/CT was performed before planned subtotal parathyroidectomy. SPECT/CT imaging revealed a 1.9-cm anterior mediastinal lesion with radiotracer uptake on both the immediate and delayed images. Surgical pathology of the lesion showed a benign thymic cyst with no parathyroid component.

St. John's Wort accelerates the liver clearance of technetium-99-sestamibi in rats.

BACKGROUND: The intense liver uptake of technetium-99-sestamibi (Tc-MIBI) and photon scattering from the liver cause problems in quantitative perfusion interpretation. Hence, Tc-MIBI is a substrate for P-glycoprotein pump; variations in P-glycoprotein levels may affect liver clearance. METHODS AND RESULTS: Adult female Wistar rats were divided into seven main groups [control and St. John's Wort (SJW) treated] and each SJW-treated group included three subgroups that were killed at 15, 30, and 45 min after Tc-MIBI injection. Treated groups received an SJW extract suspension at two doses of 100 and 400 mg/kg once daily for 5, 10, and 14 days, respectively. Tc-MIBI was injected intravenously to all rats 24 h after the final treatment. The rats were anesthetized at the mentioned time after tracer injection, and heart and liver tissues were removed, weighed, and their radioactivity was counted. One rat from each group was selected randomly for myocardial perfusion imaging. A significant increase in liver clearance and heart-to-liver ratio was observed in all SJW-treated groups compared with the control, especially at 10 days after SJW treatment. The heart radioactivity decreased in SJW-receiving groups at 14 days after SJW treatment. CONCLUSION: This study showed that SJW extract accelerates the liver clearance of Tc-MIBI and significantly reduces photon scattering from the liver.

Focal Pulmonary Uptake on 99mTc-Sestamibi Parathyroid Scintigraphy Due to Iatrogenic Microembolism.

A middle-aged woman underwent Tc-sestamibi parathyroid scintigraphy because of parathyroid disease, and a focal pulmonary uptake of Tc-sestamibi was incidentally found on both planar and SPECT/CT images without corresponding pulmonary abnormality on the CT images. After 10 days, a subsequent parathyroid scintigraphy revealed no pulmonary accumulation. Therefore, the pulmonary intense Tc-sestamibi focus that once appeared in the first scan might be an artifact of iatrogenic microembolism from injection site.

Mathematical Simulation of Transport Kinetics of Tumor-Imaging Radiopharmaceutical 99mTc-MIBI.

The proposed model describes in a quality way the process of tumor-imaging radiopharmaceutical 99mTc-MIBI distribution with taking into account radiopharmaceutical accumulation, elimination, and radioactive decay. The dependencies of concentration versus the time are analyzed. The model can be easily tested by the concentration data of the radioactive pharmaceuticals in the blood measured at early time point and late time point of the scanning, and the obtained data can be used for determination of the washout rate coefficient which is one of the existing oncology diagnostics methods.

Prognostic value of primary tumor SUVmax on F-18 FDG PET/CT compared with semi-quantitative tumor uptake on Tc-99m sestamibi breast-specific gamma imaging in invasive ductal breast cancer.

OBJECTIVE: This study aimed to evaluate the prognostic value of F-18 FDG PET/CT in comparison with Tc-99m sestamibi breast-specific gamma imaging (BSGI) and previously established clinical prognostic parameters of invasive ductal breast carcinoma (IDC). METHODS: We retrospectively included 157 female IDC patients (mean age 49.2 years, range 29.9-78.9) who underwent PET/CT and BSGI. The maximum standardized uptake value (SUVmax) and tumor to normal background ratios (TNRs) of their primary tumors were measured on PET/CT and BSGI, respectively. Univariate and multivariate survival analyses were performed to evaluate the prognostic value of the measured parameters and other clinical prognostic factors: age, menopausal status, breast density, pathologic tumor size (pTS), axillary nodal status (ANS), nuclear grade, histologic grade, hormone receptor status of estrogen (ER) and progesterone receptors (PR) and HER-2 expression. RESULTS: Among 157 patients, recurrences occurred in 22 patients (14.0 %). In univariate analyses, pTS (p < 0.0001), ANS (p < 0.0001), nuclear grade (p = 0.0046), histologic grade (p = 0.0001), ER status (p < 0.0001), PR status (p = 0.0037), HER-2 status (p = 0.0007), primary tumor SUVmax (p < 0.0001) and TNR (p = 0.0001) were significant predictors of recurrence. Among them, pTS (p = 0.0172), ANS (p = 0.0416), ER status (p = 0.0375) and primary tumor SUVmax (p = 0.0239) were independent prognostic factors in multivariate regression analysis. CONCLUSIONS: High primary tumor SUVmax of PET/CT and high TNR of BSGI were poor prognostic factors in IDC patients; in addition, primary tumor SUVmax was an independent prognostic factor along with pTS, ANS and ER status.

The importance of the incidental thyroid gland uptake during Tc-99m MIBI myocardial perfusion scintigraphy.

OBJECTIVE: The purpose of study was to investigate whether incidental thyroid gland uptake had an important during Tc-99m sestamibi (MIBI) myocardial perfusion scintigraphy (SPECT). PATIENTS AND METHODS: In the presented study, 968 consecutive patients were evaluated for the presence or absence of thyroid gland uptake in the raw data of the Tc-99m MIBI SPECT. All of the patients had thyroid gland uptake of the Tc-99m MIBI underwent laboratory evaluation of thyroid function, ultrasonographic imaging, and hystopathological examination. RESULTS: The thyroid gland uptake was detected in 14 of 968 (1.4%) consecutive patients during the evaluation of raw images of Tc-99m MIBI SPECT studies. Among these 14 patients, 4 had subacute thyroiditis, 7 multinodular goiter, 3 Graves disease by ultrasonographic imaging and hystopathological examination. TSH levels of all of these patients were < 0.01 U/ml. CONCLUSIONS: Tc-99m MIBI uptake by thyroid gland has been explained with associated clinical thyrotoxicosis. Although the primary goal of myocardial perfusion imaging is the evaluation of myocardial perfusion, the interpretation of myocardial perfusion imaging should not be limited to the heart. Because, it is possible to observe extracardiac radioactivity accumulation, which may then lead to the diagnosis of a noncardiac disease during this detailed examination.

Prognostic value of semi-quantitative tumor uptake on Tc-99m sestamibi breast-specific gamma imaging in invasive ductal breast cancer.

OBJECTIVES: This study investigated the prognostic value of preoperative breast-specific gamma imaging (BSGI) uptake measured by a semi-quantitative method in invasive ductal carcinoma (IDC). METHODS: One hundred and sixty-two women with IDC who underwent preoperative BSGI were retrospectively enrolled. The tumor-to-normal tissue ratio (TNR) was measured on BSGI and correlated with histologic prognostic factors. The prognostic impact of TNR was tested with regard to progression-free survival (PFS) and compared with established prognostic factors. RESULTS: High TNR was significantly correlated with tumor size >2 cm (p < 0.001), high nuclear grade (p = 0.04), high histologic grade (p = 0.01), axillary node positivity (p = 0.04), ER negativity (p = 0.03), HER2 positivity (p = 0.01), and high MIB-1 index (p = 0.001). Among 162 patients, 14 experienced recurrence during mean follow-up time of 34.7 ± 14.9 months. In Kaplan-Meier survival analyses, high TNR (p < 0.001), high nuclear grade (p = 0.02), high histologic grade (p = 0.007), ER/PR negativity (p = 0.003 and p < 0.001, respectively), HER2 positivity (p = 0.01), triple negativity (p = 0.02), and high MIB-1 index (p = 0.02) showed a significant relationship with poor prognosis. Among them, high TNR was an independent poor prognostic factor in a multivariate regression analysis (p = 0.01). CONCLUSIONS: High BSGI uptake measured by a semi-quantitative method was correlated with diverse poor histologic prognostic factors and was an independent poor prognostic factor in invasive ductal cancer.

Factors influencing the uptake of 99mTc-sestamibi in breast tissue on molecular breast imaging.

UNLABELLED: The purpose of this study was to evaluate the impact of changes to a patient's prandial status, metabolic status (rest vs. exercise), and peripheral blood flow (via caffeine or warming) on the uptake of (99m)Tc-sestamibi in breast tissue. METHODS: A total of 154 subjects participated in 1 of 4 study groups that evaluated the effects of 4 types of intervention on the uptake of (99m)Tc-sestamibi in breast tissue (effect of fasting, light exercise, caffeine, and peripheral warming). Molecular breast imaging was performed before and after each intervention. Count density was assessed in counts/cm(2)/MBq from the mediolateral oblique view in all studies. RESULTS: Uptake of (99m)Tc-sestamibi in breast tissue increased by approximately 25% from 6.6 counts/cm(2)/MBq in the fed state to 8.3 counts/cm(2)/MBq with fasting. Peripheral warming also resulted in an approximately 20% increase in count density from 9.1 to 10.9 counts/cm(2)/MBq. Conversely, exercise caused a 35% drop in count density relative to the resting state. Uptake did not seem to be influenced by caffeine and did not correlate with a patient's height, weight, or breast thickness. There was only a weak correlation between breast activity and body surface area. CONCLUSION: The combined effects of fasting and warming resulted in an approximately 50% increased uptake of (99m)Tc-sestamibi in breast tissue relative to that observed in a reference group to whom no preparatory instructions had been given. Optimal patient preparation before administration of (99m)Tc-sestamibi should permit a corresponding reduction in either acquisition time or required dose of (99m)Tc-sestamibi.

Implications of unexpected diffuse lung uptake on a 99mTc-sestimibi parathyroid scan.

Diffuse (99m)Tc-sestimibi uptake in the lungs is a sign of serious pathology and merits further work-up. We present a case in which diffuse lung uptake was incidentally found on a parathyroid scan.

Myocardial washout rate of resting 99mTc-Sestamibi (MIBI) uptake to differentiate between normal perfusion and severe three-vessel coronary artery disease documented with invasive coronary angiography.

OBJECTIVES: Patients with severe coronary artery disease (CAD) may present impaired mitochondrial function to enhance (99m)Tc-sestamibi (MIBI) washout from ischemic myocardium. In this study, we aimed to study the MIBI washout rate (WR) between patients with three-vessel CAD (3V-CAD) confirmed by invasive coronary angiography and healthy normal volunteers (HNV) to evaluate the potential utility of MIBI WR to differentiate between these two populations and to stratify the CAD severity. METHODS: Ten HNV (male = 5, age = 56 ± 10 years) and eight 3V-CAD patients (male = 4, age = 62 ± 8 years) with 3V lumen stenosis ≥50% were enrolled for this study. Each study subject had a resting MIBI perfusion scan at 90 min and a repeated scan at 4 h post the MIBI injection. Global WR (GWR) and regional WR (RWR) were quantified with the percentage difference of decay-corrected polar maps obtained from the two scans and compared between the HNV and 3V-CAD groups. For the 3V-CAD group, the severity of CAD was assessed with CAD severity scores (CADSS) utilizing degree and location of obstructive lesions (stenosis ≥50%) for quantification and compared with WR to evaluate the correlation between these two variables. RESULTS: Significantly higher GWR was observed in the 3V-CAD (21.1 ± 4.6 %) group than the HNV group (9.5 ± 4.9%) (p < 0.001). RWR values in left anterior descending (LAD), right coronary artery (RCA) and left circumflex (LCX) in the 3V-CAD group were also higher than those of the HNV group (LAD 20.7 ± 5.9 vs 9.4 ± 5.6, p < 0.001; RCA 21.3 ± 4.8 vs 9.2 ± 5.8, p < 0.001; LCX 20.5 ± 7.2 vs 10.1 ± 4.4, p = 0.002). Additionally, the linear correlation of GWR and total CADSS for the whole myocardium was strong and statistically significant (y = 0.86x - 1.12, r (2) = 0.73, p = 0.006). CONCLUSION: Patients with impaired mitochondrial function due to 3V-CAD had consistently higher global and regional rest (99m)Tc-sestamibi washout rates than those of healthy normal volunteers. The global rest (99m)Tc-sestamibi washout rate is a sensitive indicator to stratify the severity of 3V-CAD and to differentiate between severe 3V-CAD and normal perfusion populations.

Comparison of perfusion-metabolism mismatch in 99mTc-MIBI and 123I-BMIPP scintigraphy with cardiac magnetic resonance in patients with dilated cardiomyopathy.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging is an established method of detecting myocardial fibrosis related to prognosis in patients with dilated cardiomyopathy (DCM). Recent studies have found that (99m)Tc-methoxy-isobutyl-isonitrile (MIBI) and (123)I-15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) dual single-photon-emission computerized tomography (MIBI-BMIPP dual SPECT) can detect perfusion-metabolism mismatches. We compared MIBI-BMIPP dual SPECT with CMR findings and assessed their prognostic abilities to determine the significance of abnormal metabolism in patients with DCM. METHODS AND RESULTS: Fifty inpatients with DCM (age 58 ± 12 y; 14 female) were assessed with the use of MIBI-BMIPP dual SPECT and CMR. Perfusion-metabolism mismatches were identified mainly at the left ventricular free wall, whereas late gadolinium enhancement (LGE) was evident mostly at the septal wall. During a median follow-up of 33 months, 9 patients developed cardiac events including death, heart failure, and fatal arrhythmia. Event-free survival rates were significantly lower for patients with LGE plus a mismatch than with other abnormalities (P = .001). Among clinical and imaging variables, LGE plus a mismatch was significantly associated with cardiac events (hazard ratio 7.9, 95% confidence interval 1.8-35.6; P = .007). CONCLUSIONS: Coexisting LGE and a perfusion-metabolism mismatch accurately predict future cardiac events in patients with DCM.

Evaluation of the relationship between [18F]FDG and P-glycoprotein expression: an experimental study.

INTRODUCTION: P-glycoprotein (P-gp) is a cell-membrane-associated protein that transports a variety of drug substrates. We sought to evaluate the relationship between 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and P-gp expression using breast carcinoma Bcap37/multidrug resistant (MDR1) and Bcap37 in vitro and in vivo. METHODS: The function of P-gp expressed in Bcap37/MDR1 cells was evaluated using verapamil (VER), a classical inhibitor of P-gp. The accumulation of 99mTc-methoxyisobutylisonitrile ([99mTc]MIBI) in vitro was measured. In vivo imaging of severe combined immune deficiency (SCID) mice implanted with Bcap37 and Bcap37/MDR1 cells was performed by scintigraphy and micro-positron emission tomography (PET). RESULTS: The uptake of [99mTc]MIBI was 0.62%±0.05% in the Bcap37/MDR1 cells and 2.02%±0.28% in the Bcap37 cells. VER significantly increased the uptake of [99mTc]MIBI in the Bcap37/MDR1 cells (1.90%±0.09%) but not in the Bcap37 cells (2.15%±0.27%). In vivo, neither the Bcap37 nor Bcap37/MDR1 tumors grown in the SCID mice could be detected by [99mTc]MIBI scintigraphy. Both the Bcap37 and Bcap37/MDR1 tumors were visible by micro-PET. The mean standardized uptake value (SUV) was significantly higher in the Bcap37 tumors (1.00±0.06) than in the Bcap37/MDR1 (0.67±0.11) tumors. VER significantly increased the mean SUV in the Bcap37/MDR1 tumors (1.02±0.16) but not in the Bcap37 tumors (1.09±0.22). CONCLUSIONS: [18F]FDG combined with VER may be an effective noninvasive method of determining P-gp expression in tumors.