Preoperative imaging in primary hyperparathyroidism: Are 11 C-Choline PET/CT and 99m Tc-MIBI/123 Iodide subtraction SPECT/CT interchangeable or do they supplement each other?

OBJECTIVE: Preoperative location of hyperfunctioning parathyroid glands (HPGs) is vital when planning minimally invasive surgery in patients with primary hyperparathyroidism (PHPT). Dual-isotope subtraction scintigraphy with 99m Tc-MIBI/123 Iodide using SPECT/CT and planar pinhole imaging (Di-SPECT) has shown high sensitivity, but is challenged by high radiation dose, time consumption and cost. 11 C-Choline PET/CT (faster with a lower radiation dose) is non-inferior to Di-SPECT. We aim to clarify to what extent the two are interchangeable and how often there are discrepancies. DESIGN: This is a prospective, GCP-controlled cohort study. PATIENTS AND MEASUREMENTS: One hundred patients diagnosed with PHPT were included and underwent both imaging modalities before parathyroidectomy. Clinical implications of differences between imaging findings and negative imaging results were assessed. Surgical findings confirmed by biochemistry and pathology served as reference standard. RESULTS: Among the 90 patients cured by parathyroidectomy, sensitivity was 82% (95% confidence interval [CI]: 74%-88%) and 87% (95% CI: 79%-92%) for Choline PET and Di-SPECT, respectively, p = .88. In seven cases at least one imaging modality found no HPG. Of these, neither modality found any true HPGs and only two were cured by surgery. When a positive finding in one modality was incorrect, the alternative modality was correct in approximately half of the cases. CONCLUSION: Choline PET and Di-SPECT performed equally well and are both appropriate as first-line imaging modalities for preoperative imaging of PHPT. When the first-line modality fails to locate an HPG, additional preoperative imaging with the alternate modality offers no benefit. However, if parathyroidectomy is unsuccessful, additional imaging with the alternate modality has merit before repeat surgery.

Effect of proton pump inhibitors and H2 antagonists on gastric wall uptake in myocardial perfusion scan with 99mTc-sestamibi.

BACKGROUND: Proton pump inhibitors (PPIs) have been speculated to cause gastric wall uptake (GWU) in MPI scans. However, the uptake mechanism and prevention methods are less studied. In this prospective trial we aimed to evaluate the impact of gastroprotective medications on GWU and its solutions. METHODS: 351 consecutive patients, scheduled for 2-day rest/stress 99mTc-MIBI scan, were distributed into 5 groups. 3-7 days following the baseline rest scan, the stress scan was acquired after intervention in the trial group, consisting of patients with history of PPI intake, randomly assigned to 3 subgroups: discontinuing PPIs(A), replacement with H2 blockers (B), and continuing PPIs (C). Patients receiving H2 blockers, continued it as before (D) and the remaining patients were the control group (E). GWU was graded compared to the myocardial uptake. RESULTS: In the rest phase, all groups had significantly higher GWU compared to the control group. In the stress phase, group A had less GWU than group B (P-value < 0.05) and both of them had significantly less GWU compared to group C (P-value < 0.001). There was no significant difference between PPI discontinuation periods of 3-5 days versus 5-7 days. There was a significant association between duration of oral PPI intake, but not IV PPIs, and GWU. GWU was significantly lower with oral compared to IV PPI administration. CONCLUSION: PPIs significantly increase GWU and discontinuing them for at least 3-5 days significantly reduces GWU. H2 antagonists are a good alternative in patients who cannot tolerate dyspepsia symptoms.

99mTc-MIBI SPECT/CT SCINTIGRAPHY AND ULTRASOUND OF THE ANTERIOR NECK REGION IN DIAGNOSING PARATHYROID GLAND PATHOLOGY IN PATIENTS WITH THYROID NODULES.

Parathyroid scintigraphy with 99mTc-MIBI is an imaging technique used in nuclear medicine and performed in patients with suspected hyperparathyroidism (HPT). The objective of this study was to evaluate the role of this technique in patients who, along with suspected HPT, also have thyroid nodules. Retrospective analysis included a period of 8 years (2006-2013). The study included 91 patients with clinical or laboratory suspected HPT. Pathologic changes in parathyroid glands were demonstrated in 47 (70%) of 67 patients with positive scintigraphy. Pathologic changes in parathyroid glands were not evident in the remaining 20 (30%) patients. Out of nine patients with negative scintigraphy results but with suspected enlargement of the parathyroid gland examined by ultrasound, eight (89%) patients did not show pathologic changes in the parathyroid gland, whereas one (11%) patient had evident changes. Eight (54%) of 15 patients with suspected scintigraphy had positive ultrasound findings, as well as fine needle aspiration cytology (FNAC) findings with parathyroid hormone (PTH) determination in the aspirate. Seven (46%) patients had negative FNAC findings and PTH in the aspirate. The study showed scintigraphy to have high sensitivity (98%) in detecting patients with pathologic changes in the parathyroid glands. In patients with suspected HPT, scintigraphy needs to be combined with FNAC and PTH determination in the aspirate due to its low specificity of 28%.

Evaluation of left ventricular volumes and ejection fraction by 99mTc-MIBI gated SPECT and 18F-FDG gated PET in patients with prior myocardial infarction.

BACKGROUND: This study aimed to compare the accuracy of gated-SPECT (GSPECT) and gated-PET (GPET) in the assessment of left ventricular (LV) end-diastolic volumes (EDVs), end-systolic volumes (ESVs) and LV ejection fractions (LVEFs) among patients with prior myocardial infarction (MI). METHODS: One hundred and sixty-eight consecutive patients with MI who underwent GSPECT and GPET were included. Of them, 76 patients underwent CMR in addition to the two imaging modalities. The measurements of LV volumes and LVEF were performed using Quantitative Gated SPECT (QGS), Emory Cardiac Toolbox (ECTB), and 4D-MSPECT (4DM). RESULTS: The correlation between GPET, GSPECT, and CMR were excellent for LV EDV (r = 0.855 to 0.914), ESV (r = 0.852 to 0.949), and LVEF (r = 0.618 to 0.820), as calculated from QGS, ECTB, and 4DM. In addition, subgroup analysis revealed that EDV, ESV, and LVEF measured by GPET were accurate in patients with different extents of total perfusion defect (TPD), viable myocardium, and perfusion/metabolic mismatch. Furthermore, multivariate regression analysis identified that mismatch score was associated with the difference in EDV (P < 0.05) measurements between GPET and CMR. CONCLUSIONS: In patients with MI, LV volumes and LVEF scores measured by both GSPECT and GPET imaging were comparable to those determined by CMR, but should not be interchangeable in individual patients.

Superior performance of 18F-fluorocholine digital PET/CT in the detection of parathyroid adenomas.

OBJECTIVE: To compare detectability of hyperfunctioning parathyroid tissue (HPT) by digital and analog 18F-fluorocholine PET/CT in patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT. MATERIALS AND METHODS: Thirty-three patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT were prospectively included. All patients accepted to be scanned by digital and analog PET/CT in the same imaging session after a single injection of 18F-fluorocholine. Three nuclear medicine physicians evaluated the digital and analog PET/CT datasets to assess the detection rate of HPT. Maximum standard uptake values (SUVmax) of HPT and locoregional lymph nodes were measured in both systems. RESULTS: HPT was detected in 30/33 patients by the digital system, whereas it was detected in 22/33 patients by the analog system (p < 0.01). Moreover, in 21 of these 33 patients, both systems detected one focal 18F-fluorocholine uptake, and in one patient the digital system detected two foci. Histopathology demonstrated HPT in 32 patients and it was inconclusive in one patient. The digital PET/CT detected HPT in 29 of the 32 patients, and the analog system in 22 of the 32 (p < 0.01). All HPT suspected lesions resected and detected only by the digital system (n = 8) were < 10 mm (7.5 ± 1.3 mm), while those detected by both systems (n = 22) were > 10 mm (13 ± 3.8 mm). SUVmax of HPT lesions was significantly higher than SUVmax of locoregional lymph node independently of the PET/CT system used (4.5 ± 1.9 vs. 2.9 ± 1.3, p < 0.0001). CONCLUSIONS: Digital PET/CT offers superior performance over analog system in patients with suspected HPT and previous negative/inconclusive imaging examinations, particularly in sub-centimeter lesions. SUVmax can help in the differentiation between HTP and locoregional lymph nodes.

Effect of ursodeoxycholic acid in facilitating early hepatic clearance of radiotracer among patients undergoing 99mTc-sestamibi myocardial perfusion scintigraphy: A randomized double blind placebo controlled parallel trial.

BACKGROUND: Infra-cardiac tracer activity due to persistent hepatic activity interferes in inferior and infero-septal wall assessment during 99mTc-MIBI SPECT/CT myocardial perfusion scintigraphy (MPS) in evaluation of patients with coronary artery disease. It affects image interpretation with increased study duration. Ursodeoxycholic acid (UDCA) is known to enhance hepatic excretion of bilirubin and bile salts, though its role in enhancing the hepatic tracer clearance in facilitating cardiac imaging is not known. METHODS: This prospective, randomized double-blind, placebo controlled clinical trial of 120 patients, referred for adenosine stress or viability MPS studies were randomized 1:1 to receive either UDCA or placebo. Outcome was quantitative & qualitative improvement in imaging for better interpretation and to reduce the waiting time for scan. RESULTS: 118 participants (59 ± 11.9 years; 84 men) underwent adenosine stress MPS or viability MPS. Sixty participants had UDCA while 58 had placebo intervention. The study showed significant decrease in liver counts with improved myocardial to liver ratio at 30 and 60 minutes in adenosine stress MPS group, and marginally significant alteration in liver counts at 60 minutes in viability MPS group receiving UDCA, resulting in better images. CONCLUSION: UDCA intervention in MPS provides early and better image due to faster hepatic tracer clearance.

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.

Diagnostic performance of ultrasonography, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT in preoperative parathyroid gland localization in secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) usually requires parathyroidectomy when drug regimens fail. However, obtaining an exact preoperative map of the locations of the parathyroid glands is a challenge. The purpose of this study was to compare the diagnostic performance of US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT in patients with SHPT. METHODS: Sixty patients with SHPT who were undergoing dialysis were evaluated preoperatively by US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT. Postoperative pathology served as the gold standard. The sensitivity, specificity, and accuracy were determined for each method. Spearman correlation analysis was used to analyse the correlation of hyperplastic parathyroid calcification with serum alkaline phosphatase (ALP) and parathyroid hormone (PTH). RESULTS: A total of 229 lesions in 60 patients were pathologically confirmed to be parathyroid hyperplasia, with 209 lesions in typical sites, 15 lesions in the upper mediastinum and 5 lesions in the thyroid. A total of 88.33% (53/60) of patients had four lesions. US, early and delayed 99mTc-MIBI SPECT/CT had significantly higher sensitivity and accuracy than dual-phase 99mTc-MIBI scintigraphy (P < 0.001). Furthermore, early 99mTc-MIBI SPECT/CT had significantly higher sensitivity (P < 0.001) and accuracy (P = 0.001 and P < 0.001) than US and delayed 99mTc-MIBI SPECT/CT. In patients with ectopic hyperplastic parathyroid glands, the sensitivity of early 99mTc-MIBI SPECT/CT (90%) was significantly higher than that of US (55%) and dual-phase 99mTc-MIBI scintigraphy (50%) (P < 0.05). The Spearman correlation results showed a significant albeit weak association between calcification and both serum PTH and ALP (P = 0.002). CONCLUSION: The ability of early 99mTc-MIBI SPECT/CT to detect hyperplastic parathyroid glands in patients with SHPT is superior to that of US, dual-phase 99mTc-MIBI scintigraphy and delayed 99mTc-MIBI SPECT/CT; furthermore, dual-phase 99mTc-MIBI SPECT/CT is not essential.

The role of 99mTc-MIBI SPECT/CT in patients with secondary hyperparathyroidism: comparison with 99mTc-MIBI planar scintigraphy and ultrasonography.

BACKGROUND: This study aimed to compare the sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and ultrasonography (US) in patients with secondary hyperparathyroidism (SHPT), and to explore the factors that affect the sensitivity of 99mTc-MIBI SPECT/CT. METHODS: In this retrospective study, forty-six patients with SHPT who underwent 99mTc-MIBI planar scintigraphy, 99mTc-MIBI SPECT/CT and US were enrolled. They underwent surgery within 1 month. We compared the sensitivity of the different imaging methods based on the lesions according to the pathological results. The parathyroid lesions on 99mTc-MIBI SPECT/CT images were divided into missed diagnosis group (MDG) and non-missed diagnosis group (NMDG). We compared the lesion to background ratio (LBR), maximum diameter, volume, the mean CT Hounsfield unit values (CTmean) and location of lesions between MDG and NMDG. RESULTS: The sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and US were 70.30% versus 48.48% versus 61.82%, respectively. The sensitivity of 99mTc-MIBI SPECT/CT combined US was 79.39%, which was higher than 99mTc-MIBI SPECT/CT with significant difference (P = 0.000). On 99mTc-MIBI SPECT/CT images, the LBR, maximum diameter and volume of lesions in MDG was smaller than those in NMDG with significant difference (P < 0.001). The average LBR, maximum diameter and volume of lesions in MDG and NMDG were 3.42 ± 1.28, 9.32 ± 2.69 mm, 208.51 ± 163.22 mm3 versus 6.75 ± 5.08, 15.03 ± 4.94 mm and 863.85 ± 1216.0 mm3, respectively. CONCLUSIONS: 99mTc-MIBI SPECT/CT exhibited the highest sensitivity among the three methods. When 99mTc-MIBI SPECT/CT combined with US, the sensitivity can be further improved. Lesions with lower MIBI uptake and smaller lesions on 99mTc-MIBI SPECT/CT images were easily missed.

THE ROLE OF TUMOR-SEEKING RADIOPHARMACEUTICALS IN THE DIAGNOSIS AND MANAGEMENT OF ADRENAL TUMORS.

CONTEXT: The variety of tumor-seeking radiopharmaceuticals, which are currently in clinical use, may have a potential role as imaging agents for adrenal gland tumors, due to physiological characteristics of this organ. OBJECTIVE: The purpose of this study was to evaluate the diagnostic potential of 99mTc-HYNIC-TOC, 99mTc(V)-DMSA, and 99mTc-MIBI in the assessment of adrenal tumors, by correlating with imaging findings and histopathologic results. DESIGN: The research is designed as a cross-sectional prospective study. PATIENTS AND METHOD: The study included 50 patients with adrenal tumors (19 hormone-secreting and 31 nonfunctioning) and 23 controls without adrenal involvement. In all patients, single-photon emission computed tomography (SPECT) was performed, using qualitative and semiquantitative analysis. The tumor to non-tumor tracer uptake was conducted by using a region-of-interest technique. Adrenal to background (A/B) ratio was calculated in all cases. RESULTS: 99mTc-HYNIC-TOC scintigraphy showed a high statistical significance between A/B ratios, while other two tracers resulted in a lower sensitivity, specificity and accuracy. Futhermore, 99mTc-HYNIC-TOC could have a high diagnostic yield to detect adrenal tumors (the receiver-operating-characteristic curve analysis, A/B ratio cut-off value of 8.40). CONCLUSION: A semiquantitative SPECT analysis showed that 99mTc-HYNIC-TOC is a highly sensitive tumor-seeking agent for the accurate localization of adrenal tumors.

Radio-protective potential of lipoic acid free and nano-capsule against 99mTc-MIBI induced injury in cardio vascular tissue.

BACKGROUND: SPECT MPI (Single photon emission computed tomography myocardial perfusion imaging) is an essential tool for diagnosis of cardiovascular disease, but it also involves considerable exposure to ionizing radiation. OBJECTIVE: To determine the radioprotective potential of lipoic acid free and nano-capsule against 99mTc-MIBI-induced injury in cardiovascular tissue. METHODS: The radioprotective ability was assessed by blood count, histopathology and heart enzymes in different groups of mice. Hearts of mice from all groups were dissected and prepared for oxidative stress analysis of superoxide dismutase (SOD) and malondialdehyde (MDA). Furthermore, levels of DNA damage in heart and bone marrow cells were evaluated by alkaline comet assay technique. The same measurements were estimated after treating the mice with lipoic acid. RESULTS: Comparing mice injected by radiopharmaceutics with control group showed a significant depression in the count of white blood cells (WBC) by about 40 % at 24 &72 hrs post-radiopharmaceutical administration. Moreover, platelets count was decreased by 27% at 72 hrs post-radiopharmaceutical administration. Radiation also dropped in super oxide dismutase (SOD) and increased in activity of heart enzymes and level of MDA (Malondialdehyde). Additionally, histopathological observation was characterized by focal necrosis of cardiac myocytes. 99mTc-MIBI induced DNA damage had significant increase. Nevertheless, pretreatment with free and lipoic acid nano-capsules (LANC's) prevented the reduction induced in WBCs and platelets, and improved their counts significantly. Conversely pre-treatment with lipoic acid free and nano-capsule significantly increased the activity of SOD and decreased the level of MDA and therefore protected the cardiovascular tissues and reduced DNA strand-break, consequently and enhanced the body weight of the mice. CONCLUSIONS: These findings highlight the efficacy of lipoic acid free and nano-capsule as a radio protector.

[Investigation of the metabolic features of primary glioblastomas by Tc-MIBI SPECT/CT and evaluation of their effect on disease prognosis]. / Issledovanie metabolicheskikh osobennostei pervichnykh glioblastom metodom OFÉKT-KT s Tc-MIBI s otsenkoi ikh vliianiia na prognoz zabolevaniia.

OBJECTIVE: To study the effect of metabolic characteristics of the tumor determined by 99mTc-MIBI single-photon emission computed tomography (SPECT) and various molecular genetic features on the outcomes of combination treatment of hemispheric glioblastomas. MATERIAL AND METHODS: This single-center prospective cohort study involved 68 patients aged 25-78 years (38 males and 30 females) with primary glioblastomas. Hypermetylation of the promotor region of the MGMT gene was observed in 24 (42%) out of 57 patients. The IDH1 mutation was revealed in two (3.5%) patients. The catamnestic data were available for 66 out of 68 patients. The first SPECT/CT study was carried out before chemoradiation therapy; the second SPECT/CT study was performed after the chemoradiation therapy. In each study, quantitative measures were calculated for the early (15-30 min after the patient had received a radiopharmaceutical) and late (after 45-60 min) phases. RESULTS: The actuarial survival rates after 12 and 24 months were 69.6 and 29.1%, respectively. The median overall survival rate was 17.5 months (95% CI 12.9-20.3). Favorable prognostic factors for overall survival included the higher uptake index (UI) in the late phase compared to UI in the early phase of the first SPECT/CT study (p=0.0444), dynamics of changes in UI during the second SPECT/CT compared to baseline over 10% (p=0.0436), MGMT hypermethylation (p=0.0003), and duration of the period between surgery and initiation of chemoradiotherapy being <1 month (p=0.0008). No statistically significant correlations were revealed between the absolute UI values in the tumor and its molecular genetic features. CONCLUSION: The 99mTc-MIBI SPECT/CT can be used to predict overall survival and to plan radiation therapy of glioblastoma as it is more readily available at primary healthcare facilities than amino acid PET.

18F-Fluorocholine PET/CT in the assessment of primary hyperparathyroidism compared with 99mTc-MIBI or 99mTc-tetrofosmin SPECT/CT: a prospective dual-centre study in 100 patients.

PURPOSE: In this prospective study we compared the accuracy of 18F-fluorocholine PET/CT with that of 99mTc-MIBI or99mTc-tetrofosmin SPECT/CT in the preoperative detection of parathyroid adenoma in patients with primary hyperparathyroidism. We also assessed the value of semiquantitative parameters in differentiating between parathyroid hyperplasia and adenoma. METHODS: Both 18F-fluorocholine PET/CT and 99mTc-MIBI/tetrofosmin SPECT/CT were performed in 100 consecutive patients with biochemical evidence of primary hyperparathyroidism. At least one abnormal focus on either 18F-fluorocholine or 99mTc-MIBI/tetrofosmin corresponding to a parathyroid gland or ectopic parathyroid tissue was considered as a positive finding. In 76 patients with positive findings on at least one imaging modality, surgical exploration was performed within 6 months, and the results were related to histopathological findings and clinical and laboratory findings at 3-6 months as the standard of truth. In 24 patients, no surgery was performed: in 18 patients with positive imaging findings surgery was refused or considered risky, and in 6 patients imaging was negative. Therefore, data from 82 patients (76 undergoing surgery, 6 without surgery) in whom the standard of truth criteria were met, were used in the final analysis. RESULTS: All patients showed biochemical evidence of primary hyperparathyroidism with a mean serum calcium level of 2.78 ± 0.34 mmol/l and parathormone (PTH) level of 196.5 ± 236.4 pg/ml. The study results in 76 patients with verified histopathology and 3 patients with negative imaging findings were analysed. Three of six patients with negative imaging showed normalized serum PTH and calcium levels on laboratory follow-up at 3 and 6 months, and the results were considered true negative. In a patient-based analysis, the detection rate with 18F-fluorocholine PET/CT was 93% (76/82), but was only 61% (50/82) with 99mTc-MIBI/tetrofosmin SPECT/CT. In a lesion-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of 18F-fluorocholine PET/CT in the detection of parathyroid adenoma were 93.7%, 96.0%, 90.2%, 97.4% and 95.3%, respectively, and of 99mTc-MIBI/tetrofosmin SPECT/CT were 60.8%, 98.5%, 94.1%, 86.3% and 87.7%, respectively. Although 18F-fluorocholine PET-positive adenomatous lesions showed higher SUVmax values than the hyperplastic glands (6.80 ± 3.78 vs. 4.53 ± 0.40) in the semiquantitative analysis, the difference was not significant (p = 0.236). The mean size (measured as the length of the greatest dimension) and weight of adenomas were 15.9 ± 7.6 mm (median 15 mm, range 1-40 mm) and 1.71 ± 1.86 g (median 1 g, range: 0.25-9 g), respectively. Among the analysed parameters including serum calcium and PTH and the size and weight of parathyroid adenomas, size was significantly different between patients with negative 99mTc-MIBI/tetrofosmin SPECT/CT and those with positive 99mTc-MIBI/tetrofosmin SPECT/CT (mean size 13.4 ± 7.6 mm vs. 16.9 ± 7.4 mm, respectively; p = 0.042). CONCLUSION: In this prospective study, 18F-fluorocholine PET/CT showed promise as a functional imaging modality, being clearly superior to 99mTc-MIBI/tetrofosmin SPECT/CT, especially in the detection and localization of small parathyroid adenomas in patients with primary hyperparathyroidism. SUVmax was higher in parathyroid adenomas than in hyperplasia. However, further evaluation of this modality is needed.

Different Efflux Transporter Affinity and Metabolism of 99mTc-2-Methoxyisobutylisonitrile and 99mTc-Tetrofosmin for Multidrug Resistance Monitoring in Cancer.

BACKGROUND: Little is known about the affinity and stability of 99mTc-labeled 2-methoxyisobutylisonitrile (99mTc-MIBI) and tetrofosmin (99mTc-TF) for imaging of multiple drug resistance transporters in cancer. We examined the affinity of 99mTc-labeled compounds for these transporters and their stability. METHODS: 99mTc-MIBI and 99mTc-TF were incubated in vesicles expressing P-glycoprotein (MDR1), multidrug resistance-associated protein (MRP)1-4, or breast cancer resistance protein with and without verapamil (MDR1 inhibitor) or MK-571 (MRP inhibitor). Time activity curves of 99mTc-labeled compounds were established using SK-N-SH neuroblastoma, SK-MEL-28 melanoma, and PC-3 prostate adenocarcinoma cell lines, and transporter expression of multiple drug resistance was measured in these cells. The stability was evaluated. RESULTS: In vesicles, 99mTc-labeled compounds had affinity for MDR1 and MRP1. 99mTc-TF had additional affinity for MRP2 and MRP3. In SK-N-SH cells expressing MDR1 and MRP1, MK-571 produced the highest uptake of both 99mTc-labeled compounds. 99mTc-MIBI uptake with inhibitors was higher than 99mTc-TF uptake with inhibitors. 99mTc-TF was taken up more in SK-MEL-28 cells expressing MRP1 and MRP2 than PC-3 cells expressing MRP1 and MRP3. 99mTc-MIBI was metabolized, whereas 99mTc-TF had high stability. CONCLUSION: 99mTc-MIBI is exported via MDR1 and MRP1 (MRP1 > MDR1) at greater levels and more quickly compared to 99mTc-TF, which is exported via MDR1 and MRP1-3 (MRP1 > MDR1; MRP1, 2 > MRP3). Because 99mTc-MIBI is metabolized, clinical imaging for monitoring MDR and shorter examination times may be possible with an earlier scanning time on late phase imaging. 99mTc-TF has high stability and accurately reflects the function of MDR1 and MRP1-3.

Combined BRAFV600E analysis and 99mTc-MIBI scintigraphy can be a useful diagnostic tool in differentiated thyroid cancer patients with incomplete bio-chemical response to first radioiodine therapy (RAIT): a pilot investigation.

PURPOSE: The aim of the present study was to evaluate the possible diagnostic role of the combined performance of BRAF mutation analysis and MIBI scintigraphy in papillary thyroid cancer (PTC) patients with incomplete bio-chemical response to first radioiodine therapy (RAIT) performed for thyroid remnant ablation. METHODS: The records of 15 PTC patients with bio-chemical incomplete response to first RAIT were retrospectively analyzed. BRAFV600E analysis on primary tumor samples was obtained in all cases along with neck ultrasonography and 99mTc-MIBI scintigraphy of the neck-thorax regions at first follow-up. All patients then underwent RAIT with high radioiodine activities. A post-therapy whole-body scan (pT-WBS) was acquired 5-7 days after RAIT. RESULTS: Abnormal radioiodine uptake was found in 10 out of the 15 patients (67%, 131I+ve), while in the remaining 33%, no abnormal radioiodine uptake was detected (5/15, 131I-ve). Abnormal tracer uptake was found in 6 out of 10 131I+ve patients at 99mTc-MIBI scintigraphy (MIBI+ve). BRAFV600E mutation was not found in the majority of 131I+ve patients (9 out of 10 BRAFV600E-ve). On the contrary, in the 5 131I-ve patients, 99mTc-MIBI scintigraphy did not show any abnormal tracer uptake (MIBI-ve), while BRAFV600E mutation was present (BRAFV600E+ve). Thus, in our series, the association between MIBI-ve scintigraphy and BRAF+ve mutation was a useful diagnostic tool in predicting negative pT-WBS outcome. CONCLUSION: Albeit obtained in a small retrospective series, our results suggest that the combination of BRAFV600E+ve mutation and MIBI-ve scintigraphy may be considered a negative prognostic clue, which predicts the absence of radioiodine uptake at pT-WBS in DTC patients with incomplete bio-chemical response to first RAIT.

Characterizing Indeterminate Renal Masses with Molecular Imaging: the Role of 99mTc-MIBI SPECT/CT.

PURPOSE OF REVIEW: The majority of enhancing renal masses cannot be characterized through imaging as malignant or benign; however, such characterization could save patients from unnecessary surgery and/or biopsy and associated morbidity. Herein, we review the recent literature on the emerging use of 99mTc-MIBI SPECT/CT in preoperative differentiation of enhancing renal masses. RECENT FINDINGS: Recent reports have shown that 99mTc-MIBI SPECT/CT imaging can differentiate mitochondrial-rich, benign, or indolent renal masses from renal cell carcinoma. These studies demonstrate good correlation between a positive 99mTc-MIBI SPECT/CT scan and a pathologically proven diagnosis of renal oncocytoma and hybrid oncocytic/chromophobe tumor. In addition, there is excellent correlation between a negative scan and a diagnosis of clear cell subtype of renal cell carcinoma. Preoperative 99mTc-MIBI SPECT/CT offers a non-invasive method for differentiating renal lesions with low aggressiveness from other RCCs, in particular, clear cell renal cell carcinoma.

Lesion based diagnostic performance of dual phase 99mTc-MIBI SPECT/CT imaging and ultrasonography in patients with secondary hyperparathyroidism.

BACKGROUND: We aimed to evaluate the diagnostic performance of 99mTc-MIBI SPECT/CT and ultrasonography in patients with secondary hyperparathyroidism (SHPT), and explored the factors that affect the diagnostic performance. METHODS: 99mTc-MIBI SPECT/CT and ultrasonography were performed in 50 patients with SHPT within 1 month before they underwent surgery. Imaging results were confirmed by the pathology. Pearson correlation analysis was used to determine the correlation of PTH level with clinical data. The optimal cutoff value for predicting positive 99mTc-MIBI results was evaluated by ROC analysis in lesions diameter. RESULTS: Forty-nine patients had a positive 99mTc-MIBI imaging results and 39 patients had positive ultrasonography results. The sensitivities of 99mTc-MIBI and ultrasonography were 98.00% and 78.00%, respectively. A total of 199 lesions were resected in 50 patients. Among them, 183 lesions were proved to be parathyroid hyperplasia. On per-lesion basis analysis, the sensitivity and specificity of 99mTc-MIBI and ultrasonography were 59.34% and 75.00% vs 46.24% and 80.00%, respectively. The Pearson correlation analysis showed that the serum AKP and PTH level had a significant linear association (r = 0.699, P < 0.001). The lesion diameter was a statistically significant predictive factor in predicting positive 99mTc-MIBI SPECT/CT. The optimal cutoff value for predicting positive 99mTc-MIBI results evaluated by ROC analysis in lesions diameter was 8.05 mm. CONCLUSION: Dual phase 99mTc-MIBI SPECT/CT imaging had a higher sensitivity in patients with SHPT than ultrasonography. Therefore, using 99mTc-MIBI positioning the lesion could be an effective method pre-surgical in patients with SHPT.

The diagnostic value of 11C-methionine PET in hyperparathyroidism with negative 99mTc-MIBI SPECT: a meta-analysis.

Background 99mTc-sestamibi (MIBI) parathyroid SPECT is generally regarded as the best preoperative localizing method in patients with hyperparathyroidism (HPT). However, 99mTc-MIBI SPECT is false negative in approximately 25% of adenomas. 11C-methionine positron emission tomography (PET) has been used in HPT with negative 99mTc-MIBI SPECT scan results. Purpose To systematically review and conduct a meta-analysis of published data on the performance of 11C-methionine PET in patients with HPT with negative 99mTc-MIBI SPECT. Material and Methods A comprehensive review of the literature was performed. Pooled sensitivity and specificity of 11C-methionine PET in patients with HPT and a negative 99mTc-MIBI SPECT was calculated on a per-patient basis using receiver-operating characteristic (ROC) methodology. Results Nine studies that met all inclusion and exclusion criteria were included into our meta-analysis, comprising a total sample size of 137 patients. Pooled sensitivity and specificity of 11C-methionine PET in patients with HPT with negative or inconclusive 99mTc-MIBI SPECT scans was 86% and 86%, respectively. The area under the ROC curve was 0.87. Conclusion By merit of the high overall sensitivity, specificity, and accuracy, 11C-methionine PET can potentially complement the diagnostic workup of patients with HPT and negative or inconclusive 99mTc-MIBI SPECT. 11C-methionine PET appears to be a promising diagnostic modality in complicated cases with HPT.

Molecular imaging with (99m)Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison.

PURPOSE: To compare mutation analysis of cytology specimens and (99m)Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm. METHODS: Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and (99m)Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of (99m)Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method. RESULTS: In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. (99m)Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative (99m)Tc-MIBI scan reliably excluded malignancy. CONCLUSION: In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of (99m)Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material.

A preliminary feasibility study of simultaneous dual-isotope imaging with a solid-state dedicated cardiac camera for evaluating myocardial perfusion and fatty acid metabolism.

Simultaneous dual-isotope SPECT imaging with 201Tl and (123)I-ß-methyl-p-iodophenylpentadecanoic acid (BMIPP) is used to study the perfusion-metabolism mismatch. It predicts post-ischemic functional recovery by detecting stunned myocardium. On the other hand, (99m)Tc-MIBI is another radioisotope widely used in myocardial perfusion imaging because of its better image quality and lower radiation exposure than 201Tl. However, since the photopeak energies of (99m)Tc and (123)I are very similar, crosstalk hampers the simultaneous use of these two radioisotopes. To overcome this problem, we conducted simultaneous dual-isotope imaging study using the D-SPECT scanner (Spectrum-Dynamics, Israel) which has a novel detector design and excellent energy resolution. We first conducted a basic experiment using cardiac phantom to simulate the condition of normal perfusion and impaired fatty acid metabolism. Subsequently, we prospectively recruited 30 consecutive patients who underwent successful percutaneous coronary intervention for acute myocardial infarction, and performed (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging within 5 days after reperfusion. Images were interpreted by two experienced cardiovascular radiologists to identify the infarcted and stunned areas based on the coronary artery territories. As a result, cardiac phantom experiment revealed no significant crosstalk between (99m)Tc and (123)I. In the subsequent clinical study, (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging in all participant yielded excellent image quality and detected infarcted and stunned areas correctly when compared with coronary angiographic findings. Furthermore, we were able to reduce radiation exposure to significantly approximately one-eighth. In conclusion, we successfully demonstrated the practical application of simultaneous assessment of myocardial perfusion and fatty acid metabolism by (99m)Tc-MIBI and (123)I-BMIPP using a D-SPECT cardiac scanner. Compared with conventional (201)TlCl/(123)I-BMIPP dual-isotope imaging, the use of (99m)Tc-MIBI instead of (201)TlCl improves image quality as well as lowers radiation exposure.