99mTc-3SPboroxime: A neutral 99mTc(III) radiotracer with high heart uptake and long myocardial retention.

BACKGROUND: 99mTc-3SPboroxime is a 99mTc(III) complex with high initial heart uptake comparable to that of 99mTc-Teboroxime, but with significantly longer myocardial retention in Sprague-Dawley rats. This study was performed to demonstrate its feasibility on myocardial perfusion imaging and myocardial blood flow quantification in swine models. METHODS: Dynamic single-photon emission computed tomography (SPECT) studies with 99mTc-3SPboroxime were performed in normal (with/without dipyridamole, n = 9) and acute myocardial infarction (AMI) swine (n = 3) in comparison with 99mTc-Teboroxime and 99mTc-Sestamibi. List-mode acquisitions were immediately started after injection and continued for 15 minutes. Regions of interest were drawn on heart (infarct and remote areas of AMI swine) and liver to generate time activity curves. Heart/liver and infarct/remote radioactivity ratios were calculated. One-tissue compartment model was implemented to obtain K1 and K2 values. RESULTS: The initial heart uptake of 99mTc-3SPboroxime was close to that of 99mTc-Teboroxime, but higher than that of 99mTc-Sestamibi. 99mTc-3SPboroxime had a myocardial retention longer than that of 99mTc-Teboroxime. The heart/liver ratio of 99mTc-3SPboroxime was higher than that of 99mTc-Teboroxime at later stage (13-15 minutes post-injection). The K1 value of 99mTc-3SPboroxime was much higher than that of 99mTc-Sestamibi, and the K2 value was significantly lower than that of 99mTc-Teboroxime both at rest and dipyridamole stress (rest K1: 0.63 ± 0.11 vs 0.40 ± 0.04 mL·min-1·g-1, P = 0.027; stress K1: 0.89 ± 0.05 vs 0.54 ± 0.08 mL·min-1·g-1, P = 0.031; rest K2: 0.22 ± 0.04 vs 0.33 ± 0.11 mL·min-1·g-1, P = 0.003; stress K2: 0.31 ± 0.03 vs 0.60 ± 0.30 mL·min-1·g-1, P = 0.047). High quality SPECT images could be obtained in any of the 5 minutes windows over the first 15 minutes after injection of 99mTc-3SPboroxime in normal and AMI swine models. Apical and anterior perfusion defects were clearly visualized in AMI swine. CONCLUSION: 99mTc-3SPboroxime is a promising radiotracer for future clinical translation considering its heart uptake, heart/liver ratio and SPECT image quality, as well as the advantage over 99mTc-Sestamibi in the definition of stress flow.

Interaction between the effects of proton pump inhibitors and aspirin on gastric wall sestamibi uptake on myocardial perfusion imaging.

BACKGROUND: Increased gastric wall activity on myocardial perfusion imaging (MPI) is associated with proton pump inhibitor (PPI) therapy; however, the mechanism is unknown. We proposed a role for gastric mucosal prostaglandin synthesis and asked whether concurrent use of aspirin would antagonize this effect. METHODS: An observational study was performed of 319 patients undergoing technetium-99m sestamibi (MIBI) rest/stress MPI. We assessed the effects of taking PPIs, aspirin and their interaction on the principle outcome of clinically significant gastric wall activity. RESULTS: The outcome was observed in 13% of patients taking neither a PPI nor aspirin, 22% of those taking aspirin only, 51% taking a PPI only and 33% of those taking both. Adjusted odd ratios (95% confidence intervals) were 6.3 (CI 2.8-14.0; p < .001) for taking a PPI only, 1.8 (CI 0.8-3.9; p = .16) for taking aspirin only, and 3.0 (CI 1.4-6.5; p = .005) for taking the combination of a PPI and aspirin. There was evidence of negative statistical interaction between the two drug effects using additive (p = .006) and multiplicative (p = .016) scales. CONCLUSIONS: PPI use was strongly associated with enhanced gastric wall activity on MPI; however, concurrent aspirin appears to reduce the effect. Enhanced local prostaglandin synthesis may mediate the PPI effect.

Association of use of proton pump inhibitors and H2 antagonists with stomach wall uptake in 99mTc-methoxy-isobutyl-isonitrile (MIBI) myocardial perfusion imaging.

BACKGROUND: Stomach wall uptake (SWU) of tracer in 99mTc-MIBI myocardial perfusion imaging (MPI) occasionally leads to imaging artifacts, thereby lowering the diagnostic accuracy. It is less-studied phenomenon for possible link with proton pump inhibitors (PPIs) intake. This prospective work looked for association of SWU with PPI intake and compared its incidence with H2 antagonists (H2A) users and patients not on either gastroprotective medication. METHODS: One hundred fifty-six patients undergoing one day stress/rest 99mTc-MIBI SPECT-MPI were distributed into four groups: control group (n = 48, not on any gastroprotective medication), PPI group (n = 47, on PPI treatment), H2A group (n = 19, on H2A therapy), and intervention group (N = 42, PPI discontinued for 3 days before MPI). Poststress planar images were analyzed for clinically relevant SWU. RESULTS: Clinically relevant SWU was seen in 36% of PPI group patients compared to 8% in the control group, 10.5% in the H2A group, and 9.5% in the intervention group, respectively, with statistically significant difference. Only 1/40 patients undergoing exercise stress showed clinically relevant SWU compared to 26/116 patients undergoing adenosine stress (P = .020). CONCLUSION: Patients on PPIs scheduled for vasodilator stress MPI may discontinue PPIs for 3 days, or replace with H2A to reduce the incidence of clinically relevant SWU associated with PPI therapy.

Does the Clearance of Inhaled (99m)Tc-Sestamibi Correlate with Multidrug Resistance Protein 1 Expression in the Human Lung?

Purpose To examine the relation between the lung elimination rate of inhaled technetium 99m ((99m)Tc)-sestamibi and immunohistochemical expression of bronchopulmonary multidrug resistance protein 1 (MRP1) and permeability glycoprotein (P-gp) and assess the repeatability of the inhaled (99m)Tc-sestamibi clearance technique. Materials and Methods (99m)Tc-sestamibi is a known substrate for P-gp and MRP1, which are established cellular drug efflux transporters. The elimination rate of (99m)Tc-sestamibi from the lungs after inhalation as an aerosol has been hypothesized to be regulated by expression of these transporters. Institutional ethics committee approval was received for this prospective study. Written informed consent was obtained from all participants. The clearance of inhaled (99m)Tc-sestamibi from the lungs of 13 patients due to undergo surgery for primary lung cancer (five of 13) or spontaneous pneumothorax (eight of 13) was estimated after dynamic imaging of the lungs during a period of 40 minutes. The time taken to clear 50% of inhaled sestamibi (T1/2) was compared with a semiquantitative immunohistochemical assessment (grade 0-3) of MRP1 and P-gp expression in the lung by using parametric and nonparametric tests. The study was repeated in five participants to assess the repeatability of the technique by using a Bland Altman analysis method. Results MRP1 expression was seen in 12 of 13 patients, while P-gp expression was seen in only two. The mean (99m)Tc-sestamibi elimination rate was faster in patients (n = 6) with low levels of MRP1 expression (grade 0-1) and mean T1/2 of 105 minutes ± 20 (standard deviation), compared with those with higher levels of MRP1 expression (grade 2-3, n = 7) and mean T1/2 of 149 minutes ± 28 (P = .008). Bland-Altman analysis revealed excellent agreement between test and retest values. Conclusion Inhaled (99m)Tc-sestamibi clearance study is a repeatable technique demonstrating significant correlation with MRP1 expression in the lungs. (©) RSNA, 2016.

Background 99mTc-methoxyisobutylisonitrile uptake of breast-specific gamma imaging in relation to background parenchymal enhancement in magnetic resonance imaging.

OBJECTIVES: This study investigated factors that could affect background uptake of (99m)Tc- methoxyisobutylisonitrile (MIBI) on normal breast by breast-specific gamma imaging (BSGI). In addition, the impact of background (99m)Tc-MIBI uptake on the diagnostic performance of BSGI was further investigated. METHODS: One hundred forty-five women with unilateral breast cancer who underwent BSGI, MRI, and mammography were retrospectively enrolled. Background uptake on BSGI was evaluated qualitatively and quantitatively. Patients were classified into non-dense and dense breast groups according to mammographic breast density. Background parenchymal enhancement (BPE) was rated according to BI-RADS classification. The relationship of age, menopausal status, mammographic breast density, and BPE with background (99m)Tc-MIBI uptake was analyzed. RESULTS: Heterogeneous texture and high background uptake ratio on BSGI were significantly correlated with younger age (p < 0.001, respectively), premenopausal status (p < 0.001 and p = 0.003), dense breast (p < 0.001, respectively), and marked BPE (p < 0.001, respectively). On multivariate analysis, only BPE remained a significant factor for background MIBI uptake (p < 0.001).There was a significant reduction in positive predictive value (p = 0.024 and p = 0.002) as background MIBI uptake and BPE grade increased. CONCLUSIONS: BPE on MRI was the most important factor for background MIBI uptake on BSGI. High background MIBI uptake or marked BPE can diminish the diagnostic performance of BSGI. KEY POINTS: • Age, menopause, density, and background parenchymal enhancement affect background MIBI uptake. • BPE is an independent factor for background MIBI uptake on BSGI. • Marked BPE may impair BSGI interpretation.

Factors affecting the myocardial activity acquired during exercise SPECT with a high-sensitivity cardiac CZT camera as compared with conventional Anger camera.

PURPOSE: Injected doses are difficult to optimize for exercise SPECT since they depend on the myocardial fraction of injected activity (MFI) that is detected by the camera. The aim of this study was to analyse the factors affecting MFI determined using a cardiac CZT camera as compared with those determined using conventional Anger cameras. METHODS: Factors affecting MFI were determined and compared in patients who had consecutive exercise SPECT acquisitions with (201)Tl (84 patients) or (99m)Tc-sestamibi (87 patients) with an Anger or a CZT camera. A predictive model was validated in a group of patients routinely referred for (201)Tl (78 patients) or (99m)Tc-sestamibi (80 patients) exercise CZT SPECT. RESULTS: The predictive model involved: (1) camera type, adjusted mean MFI being ninefold higher for CZT than for Anger SPECT, (2) tracer type, adjusted mean MFI being twofold higher for (201)Tl than for (99m)Tc-sestamibi, and (3) logarithm of body weight. The CZT SPECT model led to a +1 ± 26% error in the prediction of the actual MFI from the validation group. The mean MFI values estimated for CZT SPECT were more than twofold higher in patients with a body weight of 60 kg than in patients with a body weight of 120 kg (15.9 and 6.8 ppm for (99m)Tc-sestamibi and 30.5 and 13.1ppm for (201)Tl, respectively), and for a 14-min acquisition of up to one million myocardial counts, the corresponding injected activities were only 80 and 186 MBq for (99m)Tc-sestamibi and 39 and 91 MBq for (201)Tl, respectively. CONCLUSION: Myocardial activities acquired during exercise CZT SPECT are strongly influenced by body weight and tracer type, and are dramatically higher than those obtained using an Anger camera, allowing very low-dose protocols to be planned, especially for (99m)Tc-sestamibi and in non-obese subjects.

Low-dose single acquisition rest (99m)Tc/stress (201)Tl myocardial perfusion SPECT protocol: phantom studies and clinical validation.

PURPOSE: We developed and tested a single acquisition rest (99m)Tc-sestamibi/stress (201)Tl dual isotope protocol (SDI) with the intention of improving the clinical workflow and patient comfort of myocardial perfusion single photon emission computed tomography (SPECT). METHODS: The technical feasibility of SDI was evaluated by a series of anthropomorphic phantom studies on a standard SPECT camera. The attenuation map was created by a moving transmission line source. Iterative reconstruction including attenuation correction, resolution recovery and Monte Carlo simulation of scatter was used for simultaneous reconstruction of dual tracer distribution. For clinical evaluation, patient studies were compared to stress (99m)Tc and rest (99m)Tc reference images acquired in a 2-day protocol. Clinical follow-up examinations like coronary angiography (CAG) and fractional flow reserve (FFR) were included in the assessment if available. RESULTS: Phantom studies demonstrated the technical feasibility of SDI. Artificial lesions inserted in the phantom mimicking ischaemia could be clearly identified. In 51/53 patients, the image quality was adequate for clinical evaluation. For the remaining two obese patients with body mass index > 32 the injected (201)Tl dose of 74 MBq was insufficient for clinical assessment. In answer to this the (201)Tl dose was adapted for obese patients in the rest of the study. In 31 patients, SDI and (99m)Tc reference images resulted in equivalent clinical assessment. Significant differences were found in 20 patients. In 18 of these 20 patients additional examinations were available. In 15 patients the diagnosis based on the SDI images was confirmed by the results of CAG or FFR. In these patients the SDI images were more accurate than the (99m)Tc reference study. In three patients minor ischaemic lesions were detected by SDI but were not confirmed by CAG. In one of these cases this was probably caused by pronounced apical thinning. For two patients no relevant clinical follow-up information was available for evaluation. CONCLUSION: The proposed SDI protocol has the potential to improve clinical workflow and patient comfort and suggests improved accuracy as demonstrated in the clinical feasibility study.

Abnormalities of myocardial perfusion and glucose metabolism in patients with isolated left ventricular non-compaction.

BACKGROUND: The prevalence of myocardial perfusion and glucose metabolic abnormalities and their significance in patients with isolated left ventricular non-compaction (ILVNC) have not been well investigated. METHODS: Seventeen ILVNC patients who underwent cardiac magnetic resonance (CMR) and (99m)Tc-sestamibi SPECT/fluorine-18 deoxyglucose ((18)F-FDG) PET imaging were included. Left ventricular non-compaction, regional wall motion abnormalities, left ventricular ejection fraction (LVEF), and delayed enhancement (DE) were estimated using CMR. Myocardial perfusion and metabolism were evaluated with SPECT/PET. RESULTS: Ninety-five (32.9%) segments were considered non-compacted. DE was present in 52 (18.0%) segments and 10 (58.8%) patients. The rate of occurrence of DE was significantly higher in compacted segments than in non-compacted segments (22.7% vs 8.4%, P = .003). Myocardial perfusion abnormalities were present in 92 (31.8%) segments, of which 66 were perfusion/metabolism match and 26 were perfusion/metabolism mismatch. The rate of occurrence of perfusion abnormality was similar between compacted and non-compacted segments (32.0% vs 31.6%, P = .948), but it was significantly higher in segments with DE than in those without DE (51.9% vs 27.4%, P = .001). None of the imaging features alone (non-compaction, DE, perfusion abnormalities, match or mismatch) showed significant correlations with LVEF (all P > .05). CONCLUSION: In the current study, myocardial perfusion/metabolism mismatch and match were observed in both non-compacted and compacted myocardium in ILVNC patients. Further research is warranted to determine their pathologic and clinical significance.

Comparative study of iodine-123-labeled hypericin and (99m)Tc-labeled hexakis [2-methoxy isobutyl isonitrile] in a rabbit model of myocardial infarction.

Identification of myocardial infarction (MI) by imaging is critical for clinical management of ischemic heart disease. Iodine-123-labeled hypericin (¹²³I-Hyp) is a new potent infarct avid agent. We sought to compare target selectivity and organ distribution between ¹²³I-Hyp and the myocardial perfusion agent, technetium-99m-labeled hexakis [2-methoxy isobutyl isonitrile] ((99m)Tc-Sestamibi) in rabbits with acute MI. Hypericin was radiolabeled with I using iodogen as oxidant, and (99m)Tc-Sestamibi was prepared from a commercial kit and radioactive sodium pertechnetate. Rabbits (n = 6) with 24-hour-old MI received ¹²³I-Hyp intravenously and received (99m)Tc-Sestamibi 9 hours later. They were studied by dual-isotope simultaneous acquisition micro single photon emission computed tomography/computed tomography (DISA-µSPECT/CT), tissue gamma counting (TGC), autoradiography, and histology. After purification, ¹²³I-Hyp was obtained with radiochemical purity around 99%. DISA-µSPECT/CT images showed ¹²³I-Hyp retention in infarcted but not in normal myocardium. By TGC, accumulation values reached 1.175 ± 0.096 percentage of injected dose per gram (%ID/g) and 0.028 ± 0.007%ID/g in infarcted myocardium and normal myocardium with high tracer concentration in liver, intestines, and gallbladder. (99m)Tc-Sestamibi was prepared with radiochemical purity over 95%. DISA-µSPECT/CT showed no accumulation in MI and high initial radioactivity levels in normal myocardium that were rapidly cleared as confirmed by TGC (0.011 ± 0.003%ID/g). Liver and intestines were clearly visualized. By TGC, gallbladder and kidneys show moderate (99m)Tc-Sestamibi uptake. The selectivity of ¹²³I-Hyp for infarcted myocardium and (99m)Tc-Sestamibi for normal myocardium was confirmed. ¹²³I-Hyp distribution in rabbits is characterized by hepatobiliary excretion. (99m)Tc-Sestamibi undergoes hepatorenal elimination.

A pharmacodynamic study of the P-glycoprotein antagonist CBT-1® in combination with paclitaxel in solid tumors.

BACKGROUND: This pharmacodynamic trial evaluated the effect of CBT-1® on efflux by the ATP binding cassette (ABC) multidrug transporter P-glycoprotein (Pgp/MDR1/ABCB1) in normal human cells and tissues. CBT-1® is an orally administered bisbenzylisoquinoline Pgp inhibitor being evaluated clinically. Laboratory studies showed potent and durable inhibition of Pgp, and in phase I studies CBT-1® did not alter the pharmacokinetics of paclitaxel or doxorubicin. METHODS: CBT-1® was dosed at 500 mg/m2 for 7 days; a 3-hour infusion of paclitaxel at 135 mg/m2 was administered on day 6. Peripheral blood mononuclear cells (PBMCs) were obtained prior to CBT-1® administration and on day 6 prior to the paclitaxel infusion. (99m)Tc-sestamibi imaging was performed on the same schedule. The area under the concentration-time curve from 0-3 hours (AUC(0-3)) was determined for (99m)Tc-sestamibi. RESULTS: Twelve patients were planned and enrolled. Toxicities were minimal and related to paclitaxel (grade 3 or 4 neutropenia in 18% of cycles). Rhodamine efflux from CD56+ PBMCs was a statistically significant 51%-100% lower (p < .0001) with CBT-1®. Among 10 patients who completed imaging, the (99m)Tc-sestamibi AUC(0-3) for liver (normalized to the AUC(0-3) of the heart) increased from 34.7% to 100.8% (median, 71.9%; p < .0001) after CBT-1® administration. Lung uptake was not changed. CONCLUSION: CBT-1® is able to inhibit Pgp-mediated efflux from PBMCs and normal liver to a degree observed with Pgp inhibitors studied in earlier clinical trials. Combined with its ease of administration and lack of toxicity, the data showing inhibition of normal tissue Pgp support further studies with CBT-1® to evaluate its ability to modulate drug uptake in tumor tissue. DISCUSSION: Although overexpression of ABCB1 and other ABC transporters has been linked with poor outcome following chemotherapy efforts to negate that through pharmacologic inhibition have generally failed. This is thought to be a result of several factors, including (a) failure to select patients with tumors in which ABCB1 is a dominant resistance mechanism; (b) inhibitors that were not potent, or that impaired drug clearance; and (c) the existence of other mechanisms of drug resistance, including other ABC transporters. Although an animal model for Pgp has been lacking, recent studies have exploited a Brca1(-/-); p53(-/-) mouse model of hereditary breast cancer that develops sporadic tumors similar to cancers in women harboring BRCA1 mutations. Treatment with doxorubicin, docetaxel, or the poly(ADP-ribose) polymerase inhibitor olaparib brings about shrinkage, but resistance eventually emerges. Overexpression of the Abcb1a gene, the mouse ortholog of human ABCB1, has been shown to be a mechanism of resistance in a subset of these tumors. Treating mice with resistant tumors with olaparib plus the Pgp inhibitor tariquidar resensitized the tumors to olaparib. Although results in this animal model support a new look at Pgp as a target, in this era of "targeted therapies," trial designs that directly assess modulation of drug uptake, including quantitative nuclear imaging, should be pursued before clinical efficacy assessments are undertaken. Such assessment should be performed with compounds that inhibit tissue Pgp without altering the pharmacokinetics of chemotherapeutic agents. This pharmacodynamic study demonstrated that CBT-1®, inhibits Pgp-mediated efflux from PBMCs and normal liver.

[Comparison of the biodistribution of four contrast agents in nude mice bearing NCI-H358 human lung cancer and evaluation of their value in diagnostic imaging].

OBJECTIVE: To compare the uptake of four contrast agents: (99)Tc(m)-RGD-4CK, (99)Tc(m)-N(NOET)(2), (99)Tc(m)-MIBI and (18)F-FDG in Bal B/c nude mice bearing human non-small cell lung cancer NCI-H358 and evaluate their diagnostic value in low-metabolic lung cancer. METHODS: Human bronchioloalveolar carcinoma NCI-H358 cells were subcutaneously inoculated in Bal B/c nude mice to establish mouse models bearing human lung cancer. Twenty tumor-bearing nude mice were given injection of the four contrast agent, respectively, 5 mice in each group. SPECT imaging and biodistribution of the 4 tracers in the tumor-bearing nude mice were performed. The ratios of tumor to non-tumor (T/NT) of the tracers were compared. RESULTS: The results from semi-quantification of the planar image and assessment of biodistribution showed that tumor to contralateral muscle activity ratios (T/NT) of the four tracers had statistically significant difference between each two of the four tracer groups of tumor-bearing mice (P < 0.001), with a highest value of T/NT ratio in the (99)Tc(m)-RGD-4CK group. CONCLUSIONS: NCI-H358 tumors show a higher uptake of (99)Tc(m)-RGD-4CK than (18)F-FDG. It suggests that when diagnosing a well-differentiated lung cancer such as bronchioloalveolar carcinoma, the contrast agent (99)Tc(m)-RGD-4CK may be more sensitive than (18)F-FDG, and it may become a promising contrast agent in tumor imaging diagnosis.

A single (99m)Tc-MIBI study to predict response to neoadjuvant treatment in sarcoma patiens.

Technetium-99m methoxy isobutyl isonitrile ((99m)Tc-MIBI) was used as a tumour imaging agent to predict the response of neoadjuvant treatment in patients with bone and soft tissue sarcoma. Our study included 31 patients (M:F = 23:8), 17 having osteosarcomas and 14 with soft-tissues sarcomas. Scintigraphy with (99m)Tc-MIBI was performed before the initiation of the neoadjuvant treatment. Static images were acquired at 10 and 60min post-injection and lesion to normal (L/N) ratios and washout rates (WR%) were calculated. Tumour response was assessed by detecting percent necrosis in a surgically resected specimen. Responses were correlated and compared with WR%. Percentage of tumour necrosis was 71.35±20.20% (mean±SD) with eight good and 23 poor responses. On visual analysis, 16 showed homogeneous, 11 heterogeneous and 4 doughnut shaped pattern of uptake. Seventy five percent of good responders had homogeneous uptake. Early and delayed L/N ratios were significantly different in both good and poor responders (P=0.006 and P<0.001, respectively) but correlated poorly with the tumour necrosis values in the specimen (R=0.23 and 0.06 respectively). Mean washout rate was 26.13±11.25% (median = 29%) and there was weak correlation between tumour necrosis and WR% (r=-0.32, P=0.029). The mean WR% of good responders was 15.0±10.0% and that of poor responders was significantly higher (30.1±8.8%, P=0.003). Good responders by 88% were below the median cut-of value. In conclusion WR% of (99m)Tc-MIBI may be used before surgery to identify poor responders to neoadjuvant treatment in patients with bone and soft tissue sarcomas.

Noninvasive quantification of coronary endothelial function by SPECT imaging in children with a history of Kawasaki disease.

PURPOSE: The feasibility of coronary function estimation by single photon emission computed tomography (SPECT) has been recently demonstrated. The aim of this study was to apply SPECT imaging in patients with previous Kawasaki disease (KD) to assess the coronary functional status at long-term follow-up of the acute phase of the disease. METHODS: Sixteen children with a history of KD underwent 99mTc-sestamibi imaging at rest and during the cold pressor test (CPT). Myocardial blood flow (MBF) was estimated by measuring first transit counts in the pulmonary artery and myocardial counts from SPECT images. Coronary endothelial function was expressed as the ratio of the CPT to rest MBF. RESULTS: Six KD patients without coronary artery lesions served as controls and ten with coronary artery aneurysms during the acute phase of the disease were separated into two groups: group 1 (n=4) with regressed and group 2 (n=6) with persistent aneurysm at follow-up. The estimated coronary endothelial function was higher in controls compared to patients with coronary artery aneurysms (2.5±0.3 vs 1.7±0.7, p<0.05). A significant difference in coronary endothelial function among groups was found (F=5.21, p<0.02). Coronary endothelial function was higher in patients of group 1 than in those of group 2 (1.9±0.6 vs 1.4±0.7, p<0.02). CONCLUSION: SPECT may be applied as a noninvasive method for assessing coronary vascular function in children with a history of KD, demonstrating an impaired response to the CPT, an endothelial-dependent vasodilator stimulus. These findings reinforce the concept that coronary endothelial dysfunction may represent a long-term sequela of KD.

Evaluation of (99m)technetium-mebrofenin and (99m)technetium-sestamibi as specific probes for hepatic transport protein function in rat and human hepatocytes.

PURPOSE: This study characterized 99mTc-Mebrofenin (MEB) and 99mTc-Sestamibi (MIBI) hepatic transport and preferential efflux routes (canalicular vs. basolateral) in rat and human sandwich-cultured hepatocytes (SCH). METHODS: 99mTc-MEB and 99mTc-MIBI disposition was determined in suspended hepatocytes and in SCH in the presence and absence of inhibitors and genetic knockdown of breast cancer resistance protein (Bcrp). RESULTS: The general organic anion transporting polypeptide (Oatp/OATP) inhibitor rifamycin SV reduced initial 99mTc-MEB uptake in rat and human suspended hepatocytes. Initial 99mTc-MIBI uptake in suspended rat hepatocytes was not Na+-dependent or influenced by inhibitors. Multidrug resistance-associated protein (Mrp2/MRP2) inhibitors decreased 99mTc-MEB canalicular efflux in rat and human SCH. 99mTc-MEB efflux in human SCH was predominantly canalicular (45.8 +/- 8.6%) and approximately 3-fold greater than in rat SCH. 99mTc-MIBI canalicular efflux was similar in human and rat SCH; basolateral efflux was 37% greater in human than rat SCH. 99mTc-MIBI cellular accumulation, biliary excretion index and in vitro biliary clearance in rat SCH were unaffected by Bcrp knockdown. CONCLUSION: 99mTc-MEB hepatic uptake is predominantly Oatp-mediated with biliary excretion by Mrp2. 99mTc-MIBI appears to passively diffuse into hepatocytes; biliary excretion is mediated by P-gp. The SCH model is useful to investigate factors that may alter the route and/or extent of hepatic basolateral and canalicular efflux of substrates.

99mTc-sestamibi scan differentiates tumor from other contrast enhancing tissue in choroid plexus tumors.

Choroid plexus tumors are rare brain tumors which account for 0.4% to 0.6% among brain tumors. Tumor resection is known to be of large prognostic impact, and re-resection of residual tumors is a part of standard care. However, after multiple resections it can become difficult to differentiate tumor from reactive tissue. 99mTC-sestamibi scans may assist in differentiating neoplastic (99mTC-sestamibi positive) from non-neoplastic tissue (99mTC-sestamibi negative). Previous literature showed sestamibi to be helpful in detecting residual choroid plexus tumors resulting in further resection. Here, we report the first case to show that sestamibi scans can also help with the opposite decision.

Initial and delayed stress phase imaging in a single-injection double-acquisition SPECT. The potential value of early 99mTc-MIBI redistribution in assessment of myocardial perfusion reversibility in patients with coronary artery disease.

UNLABELLED: Some studies reported that 99mTc-MIBI may redistribute in ischaemic myocardium and this phenomenon may have potential role for better assessment of viability by delayed 99mTc-MIBI imaging. Some studies also suggested that infusion of low dose dobutamine during delayed imaging may enhance the value of 99mTc-MIBI imaging for evaluation of viability. The aim of this study is to determine whether the observed changes of perfusion defects on delayed images are caused by early radiotracer redistribution or as a result of reversal partial volume effect secondary to inotropic stimulation. PATIENTS, METHODS: 89 patients with angiographically proven coronary artery disease (CAD) were enrolled in this randomized clinical trial study. In all cases, gated-SPECT images were obtained 60 minutes after stress with dipyridamole injection. Subsequently the patients were randomly allocated in two groups and the second imaging was performed at 120th minute during low dose dobutamine (dobutamine group; 45 cases) or placebo infusion (placebo group; 44 cases). Difference between summed stress score of the first (SSS1) and second (SSS2) stress images (DeltaSSS) was considered as a marker of reversibility in single-injection double-acquisition (SIDA) protocol. Also summed difference score (SDS) was recorded as a marker of reversibility in standard stress/rest, double-injection double-acquisition (DIDA) protocol. DeltaSSS of the two studied groups were compared. Also the correlation and agreement between DeltaSSS and SDS were analyzed. RESULTS: A significant difference was found between SSS1 (median 15, range 0-48) and SSS2 (median 11, range 0-42) in total patients (p < 0.0001). A significant correlation was noted between DeltaSSS and SDS in dobutamine group (r = 0.58, p = 0.002) as well as in placebo group (r = 0.57, p < 0.0001). Considering DIDA protocol as a standard reference method, the influence of dobutamine infusion was not shown to be significantly different from the placebo effect on the magnitude of fixed or reversible perfusion defects in SIDA protocol. CONCLUSION: The changes in the magnitude of the perfusion defects may occur in the first hours of 99mTc-MIBI injection in the stress phase imaging. These changes correlate well and are in agreement with perfusion improvement on the rest images. This phenomenon may be independent of improvement in myocardial function, in more delayed imaging or following inotropic augmentation, and thus is likely due to 99mTc-MIBI redistribution. This may open new technical and clinical aspects and potentials for 99mTc-MIBI imaging.

Influence of extracardiac activity and perfusion abnormalities on myocardial perfusion gated SPECT parameters: interobserver analysis.

OBJECTIVE: Extracardiac activity (ECA) may affect interpretation of gated SPECT myocardial perfusion studies (MPSs). To solve this problem, available softwares include myocardial edge delimitation. PURPOSE: To evaluate the influence of ECA in automatic myocardial edge detection under normal conditions and with abnormal perfusion and also evaluate the reproducibility of semi-automatic processing. METHODS: A total of 100 MPSs, 50 with ECA, were analyzed. Each subgroup included 25 cases with perfusion abnormalities. The cases were processed automatically and by 4 independent operators with different levels of experience. Commercial QGS and QPS softwares were used with tools to mask and relocate the left ventricle area. Functional parameters (final diastolic and systolic volumes and ejection fraction) and perfusion parameters such as the reversibility perfusion score and rest perfusion defect extension were analyzed. The data were compared with Pearson's correlation and Student's test. RESULTS: Interobserver correlation significantly worsened with the presence of ECA and was moderately affected by perfusion abnormalities. More experienced observers presented better correlation. Reproducibility was greater for the functional perfusion parameters, independently of the observer's experience. CONCLUSIONS: ECA significantly affects automatic edging delimitation, affecting the MPS values. Interobserver reproducibility with manual processing was more altered regarding functional parameters than in the perfusion scores. Perfusion abnormalities did not interfere with software reproducibility, and when present, better correlation was found. If ECA is not present, manual intervention should be avoided.