Comparison of technetium-99m-sestamibi scintimammography with contrast-enhanced MRI for diagnosis of breast lesions

A carboxylesterase [2,3,4,6-tetra-O-acetyl-1-[(N-acetyl-N-phenylamino)oxy]-1-deoxy-beta-D-g lucopyranoside (GPA) O-deacetylase] from a culture product of Aspergillus oryzae (Taka diastase) was purified 8500-fold with a yield of 3%. The molecular mass of the purified enzyme was shown to be 35 +/- 1 kDa by SDS/PAGE. The enzyme shows a selective O-deacetylation activity of GPA to give the fully O-deacetylated glucoside. Among the substrates tested, the enzyme did not hydrolyze benzoyl and phenylacetyl esters and acetamides. In the hydrolysis of p-nitrophenyl esters, the acyl preference is acetyl > propionyl > butyryl, judging from the Vmax/Km values. A good correlation between log(Vmax/Km) and the Taft's Es constant of the alkyl group of the acyl moiety was obtained. The optimum pH was around 7.3 at 37 degrees C, and the enzyme was inhibited by mercuric chloride, p-chloromercuribenzoate and diisopropyl fluorophosphate. This enzyme should be useful for the selective removal of acetyl groups that serve to protect hydroxyl groups during carbohydrate synthesis.     

Using gated technetium-99m-sestamibi SPECT to characterize fixed myocardial defects as infarct or artifact

Perfusion-scan fixed defects may result from soft tissue attenuation, decreasing test specificity for coronary disease and myocardial infarction (MI). Gated 99mTc-sestamibi SPECT may help differentiate MI from artifact since fixed defects with decreased function (wall motion and thickening) probably represent MI, whereas attenuation artifacts either have normal function or at least do not demonstrate markedly reduced function. METHODS: Ungated resting and gated stress 99mTc-sestamibi SPECT was performed in 551 consecutive patients referred for evaluation of coronary disease. From resting and summed gated stress images, 180 patients (33%) were identified with isolated fixed defects. Function of the defects was assessed subjectively from gated stress images and results were correlated with clinical (history and/or ECG Q-waves) evidence of MI. RESULTS: Of 102 patients with fixed defects and clinical MI, 98 (96%) had abnormal defect function. Of 78 patients with no clinical MI, 18 (23%) had decreased function of the defect, possibly indicating silent MI. In 60 of the 78 patients (77%) with no clinical MI, defect function was normal. Because most (91%) of fixed defects with normal systolic function occurred in women with anterior fixed defects (48%) or men with inferior fixed defects (43%), these were most likely attenuation artifacts. By reclassifying patients with fixed defects and normal function as normal, patients with unexplained fixed defects (no clinical MI) decreased from 14% to 3%. CONCLUSION: Gating provides a valuable adjunct to 99mTc-sestamibi SPECT in characterizing fixed defects and potentially improving test specificity.     

Comparison of technetium-99m-MIBI and technetium-99m-tetrofosmin uptake by musculoskeletal sarcomas

The development of molecular biology techniques has enabled us to clone the genetic sequence of three new hepatitis viruses, namely, hepatitis C virus, hepatitis E virus and hepatitis G, or GBV-C virus in the last decade. Hepatitis C virus (HCV) is now known to account for the majority of the parenterally transmitted non-A, non-B hepatitis and hepatitis E virus (HEV) is the major cause of the epidemics of enterally transmitted non-A, non-B hepatitis in the less developed countries, mainly through contaminated water supplies. While 80% of those who were infected with HCV will become chronic carriers, there is no known chronic carrier state for HEV. To date, 6 major genotypes of HCV were identified, with various variants of genotype 6 described in Southeast Asia. In Singapore, the majority of our chronic hepatitis C patients are infected with genotype 1. The seroprevalence rate of HEV is 10% to 14% in Singapore. This probably reflects our suboptimal sanitary condition in the past rather than a reflection of a currently high HEV infection rate in our population. However, local cases of acute hepatitis E have been reported. As for the most recently cloned hepatitis G virus, its aetiologic role in the remaining cases of non-A, non-B hepatitis is still unclear. Some preliminary evidence suggests that it may be just an innocent bystander with limited pathogenicity and it certainly cannot account for all the remaining cases of non A-E hepatitis. Hence, the search for yet another hepatitis virus continues.     

Monitoring response to therapy with thallium-201 and technetium-99m-sestamibi SPECT in nasopharyngeal carcinoma

This study prospectively assessed the value of 201Tl and 99mTc-sestamibi (MIBI) SPECT in monitoring disease regression/progression as compared with MRI findings in patients with nasopharyngeal carcinoma (NPC) having radiotherapy with or without chemotherapy. METHODS: Eighteen patients (age range 15-78 yr, mean 45 yr) had consecutive SPECT imaging using a dual-head gamma camera after the injection of 111 MBq 201Tl and 555 MBq MIBI before therapy and at 3 mo and 6 mo after completion of therapy. A total of 106 SPECT studies was correlated with contemporaneous MRI studies. Tumor-to-background ratios were obtained on coronal slices. Visually detectable lesions in the region of the nasopharynx and cervical lymph nodes were considered positive for residual disease. The gold standard for the presence of disease was the combination of repeat MRI scans, endoscopic examination and clinical evaluation performed 12-15 mo after completion of therapy. RESULTS: MIBI-SPECT proved superior to both 201Tl SPECT and MRI after 3 or 6 mo follow-up in predicting complete response. Accuracy rates in the detection of residual disease in the nasopharynx are 39%, 72% and 89% for MRI, 201Tl and MIBI, respectively, for the 3-mo evaluation; 71%, 71% and 94% for MRI, 201Tl and MIBI, respectively, for the 6-mo evaluation. CONCLUSION: MIBI SPECT could be used as a screening test in predicting response to therapy in patients with NPC.     

Clinical validation of the influence of P-glycoprotein on technetium-99m-sestamibi uptake in malignant tumors

We prospectively studied 48 patients with either breast cancer (30 patients) or lung cancer (18 patients) to ascertain the relationship between the degree of accumulation of 99mTc-sestamibi and the expression of p-glycoprotein in tumor tissues. METHODS: During initial presentation (37 patients) or post-therapy evaluation (11 patients), the patients underwent contemporaneous 99mTc-sestamibi imaging and biopsy (30 patients) or surgery (18 patients). The interval between surgery/biopsy and imaging varied between 3 and 15 days. All patients had radiologically detectable tumors. Immunohistochemical studies were performed on paraffin sections using a monoclonal antibody, JSB-1, developed against the internal epitope of p-glycoprotein. Tumor-to-background ratios were correlated with the level of p-glycoprotein expression determined by immunohistochemical studies. RESULTS: Our results showed an inverse correlation between the tumor-to-background ratios of 99mTc-sestamibi and the density of p-glycoprotein expression in tumor tissues. The values for the tumor-to-background ratios were significantly lower for those tumors expressing p-glycoprotein at high levels than those with scattered and no expression (p < 0.01 and p < 0.001, respectively). CONCLUSION: Although our results warrant further studies at the molecular level using PCR techniques after the extraction of mRNA, our data strongly suggest that 99mTc-sestamibi imaging is useful to noninvasively determine the presence of multidrug resistance in patients with malignant tumors.     

Intra-individual differences between technetium-99m-HMPAO and technetium-99m-ECD in the normal medial temporal lobe

Regional distributions of 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO) and 99mTc-ethyl cysteinate dimer (99mTc-ECD) were compared in the normal brain. METHODS: Six paid, healthy volunteers (mean age 26 yr) had high-resolution neuroperfusion SPECT using both 99mTc-HMPAO and 99mTc-ECD on separate days. RESULTS: Regional distribution of the two tracers differed. Technetium-99m-HMPAO accumulated more in the thalamus, frontal lobe, temporal lobe and cerebellum than 99mTc-ECD, which accumulated more in the occipital and parietal lobes. There was a considerable difference in the accumulation of the two tracers in the medial temporal lobe. The percent accumulations of 99mTc-HMPAO and 99mTc-ECD in the medial temporal lobe compared with the mean global cerebral cortical accumulation were 93.9% +/- 2.4% and 83.1% +/- 4.1% (mean +/- s.d.), respectively. CONCLUSION: The results suggest that 99mTc-HMPAO and 99mTc-ECD require specific and separate criteria for diagnosing temporal lobe pathologies, such as dementia and temporal lobe epilepsy.     

Comparative myocardial uptake of technetium-99 m sestamibi and technetium-99m tetrofosmin one hour after stress injection

Technetium-99m sestamibi and 99mTc-tetrofosmin are at present the preferred tracers for simultaneous assessment of myocardial perfusion and function by gated single-photon emission tomography (SPET). The aim of this work was to compare sestamibi and tetrofosmin myocardial uptake 1 h after stress injection. Consecutive unselected patients were studied either with sestamibi or with tetrofosmin on a random basis, until at least 100 patients had been enrolled for each gender and tracer. Stress was obtained by dipyridamole or exercise or combined dipyridamole + exercise; in the latter cases, exercise was sustained for at least 1.5 min after tracer injection. Injected activity was similarly adjusted to body weight. For each patient, imaging began 60-75 min after injection. All SPET projections were summed; due to the acquisition technology ("roving zoom", i.e. a mobile zoom), the heart always appeared at the centre of the frame in all projections and in the sum image. Thus minimal lung background contamination could be assumed in an elliptic region of interest placed over the heart on the sum image. Three indexes were analysed: total myocardial counts (Sum), mean myocardial pixel (Mean) and maximum myocardial pixel (Max). Four patient groups were analysed: males with sestamibi or tetrofosmin (MS: n = 189 and MT: n = 157), females with sestamibi or tetrofosmin (FS: n = 101 and FT: n = 104). MS and MT groups were comparable for physical variables, maximum heart rate and stress type, as were the FS and FT groups. Sum, Mean and Max were significantly higher with sestamibi (P = 0.0001 by ANOVA). Comparing MS vs MT and FS vs FT, mean values +/- SD were as follows: for Sum (kcounts) 750+/-184 vs 652+/-166, and 707+/-202 vs 594+/-189; for Mean (counts) 4517+/-1171 vs 4107+/-898, and 4908+/-1119 vs 4144+/-1025; and for Max (counts) 6471+/-1654 vs 5794+/-1312, and 7318+/-1886 vs 6152+/-1684. The mean gain with sestamibi was +15%, +10% and +12% in males, and +19%, +18% and +19% in females. Similar differences were found within each stress type subgroup. No gender-specific effect was found for Mean, so the overall mean gain was calculated for Mean: +13% for sestamibi vs tetrofosmin. These findings are consistent with other published smaller sample series. Possible differences between tracers with regard to residual activity in syringes were ruled out by an additional experiment. In summary, we found significantly higher myocardial counts with sestamibi than with tetrofosmin, in males as well as in females.     

Comparison of technetium-99m-ll-EC isomers in rats and humans

Technetium-99m-L,L-ethylenedicysteine (99mTc-LL-EC) is a new renal imaging agent with pharmacokinetic properties reported to be slightly superior to those of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3); however, to better define the potential of the enantiomer 99mTc-DD-EC and the diastereomer 99mTc-DL-EC as renal imaging agents, we compared the three EC stereoisomers with 131I-orthoiodohippurate (OIH) in a series of rats and humans. METHODS: Each 99mTc-EC stereoisomer was coinjected with OIH in six Sprague-Dawley rats for measurements of clearance and extraction fraction. Each stereoisomer was also coinjected with OIH in three human volunteers followed by sequential imaging, plasma clearance measurements and timed urine collections. RESULTS: Technetium-99m-DD-EC had the highest clearance and extraction efficiency in rats (p < or = 0.02). In humans, image quality was good with all three agents. The clearance ratio (EC/OIH) was 82% +/- 8% for 99mTc-DD-EC compared to 70% +/- 3% and 40% +/- 5% for 99mTc-LL-EC and 99mTc-DL-EC, respectively. Technetium-99m-DD and 99mTc-LL-EC were excreted more rapidly than 99mTc-DL-EC. CONCLUSION: Technetium-99m-DD-EC has excellent imaging properties and the data suggest that its clearance may approach that of OIH more closely than any other 99mTc renal agent. A potential limitation is the fact that both 99mTc-DD and LL-EC exist in dianionic (80%) and monoanionic (20%) forms at physiological pH and it is unlikely that these two forms have the same clearance or protein binding affinity.     

Discordance of technetium-99m-HMPAO and technetium-99m-ECD SPECT in herpes simplex encephalitis

Technetium-99m-hexamethyl propyleneamine oxime (HMPAO) and 99mTc-ethyl cysteinate dimer (ECD) accumulate in brain tissue in proportion to regional cerebral blood flow in healthy subjects and in patients with a variety of neurological diseases. We report on four patients with herpes simplex encephalitis and the discordance between these two approved cerebral perfusion imaging radiopharmaceuticals. CONCLUSION: SPECT images showed unilateral regional increase of 99mTc-HMPAO uptake and decrease of 99mTc-ECD uptake in the affected temporal lobe.     

Comparison between thallium-201 and technetium-99m-tetrofosmin uptake with sustained low flow and profound systolic dysfunction

Technetium-99m-tetrofosmin uptake was compared to that of 201Tl in the setting of low flow and systolic dysfunction. METHODS: In nine open-chested dogs, a severe left anterior descending (LAD) coronary artery stenosis resulted in a 54.3% mean flow reduction and decreased left ventricular thickening from 21% +/- 1% to -3 +/- 2%. After 30 min, 37 MBq (1 mCi) of 201Tl and microspheres were injected and initial and 2-hr redistribution images acquired. Two hours later, 370 MBq (10 mCi) of 99mTc-tetrofosmin and microspheres were injected and an image was obtained. LAD: left circumflex (LCX) count ratios for both tracers and flows were calculated by well counting postmortem, and 201Tl and 99mTc-tetrofosmin defect magnitudes were determined by quantitative image analysis. RESULTS: LAD:LCx flow ratios were similar during 201Tl and 99mTc-tetrofosmin injections (0.48 +/- 0.04 versus 0.49 +/- 0.05, p = n.s.). Final 201Tl activity (0.66 +/- 0.04) was significantly higher than 99mTc-tetrofosmin (0.55 +/- 0.05; p < 0.05). LAD/LCx 99mTc-tetrofosmin image defect count ratio was similar to 201Tl defect count ratio on the initial rest 201Tl scan (0.57 +/- 0.03 versus 0.56 +/- 0.02, p = ns), but significantly less than 201Tl defect count ratio at 2 hr (0.57 +/- 0.03 versus 0.65 +/- 0.02, p < 0.05). CONCLUSION: In a low-flow model with profound systolic dysfunction, myocardial 99mTc-tetrofosmin uptake ( > 50%) reflective of viability was observed in the asynergic zone perfused by the stenotic LAD.     

Limited clinical diagnostic specificity of technetium-99m stannous pyrophosphate myocardial imaging in acute myocardial infarction

To test the sensitivity and specificity of technetium-99m stannous pyrophosphate myocardial imaging in the diagnosis of acute myocardial infarction, myocardial scintigrams were performed in 115 patients. Positive scintigrams were found in all 48 patients with acute myocardial infarction; uptake was localized in 29 patients with transmural infarction and diffuse in 2 patients with transmural infarction and in the remaining 17 patients with subendocardial myocardial infarction. Positive scintigrams were also found in 31 of 67 patients without clinical evidence of acute myocardial infarction. Diffusely positive scintigrams were found in 3 of 3 patients with unstable angina pectoris, 7 of 30 patients with stable angina pectoris, 4 of 13 patients who had undergone aortocoronary bypass surgery, 4 of 4 patients with congestive cardiomyopathy and 1 patient studied 1 day after direct current cardioversion. Localized uptake of 99mTc-pyrophosphate was found in 9 of 10 patients with left ventricular aneurysm and in 3 of 13 patients after aortocoronary bypass surgery. All four patients with atypical chest pain and two patients with pericarditis had normal scintigrams. Our data confirm the previously reported sensitivity of 99mTc-pyrophosphate imaging in detection of acute myocardial infarction but indicate that positive scintigrams are not specific for this entity.     

Anomalies in hepatobiliary excretion of technetium-99m-MAG3 preparations

Technetium-99m-MAG3 is accepted as a renal tubular function agent. However, sporadic liver and gall bladder visualisation during its clinical use is clearly a disadvantage. HPLC-purified 99mTc-MAG3 samples exhibited appreciable hepatobiliary uptake (7%), and an elevated level of such uptake was observed in unpurified kit preparations, which was stated to be associated with the excretory property of the radiolabeled kit impurities. To verify this we attempted to quantitate the hepatobiliary uptake of the kit preparations with that of its radiolabeled components. The contribution of each component toward hepatobiliary uptake of the sample was calculated from their abundance in the chelate mixture and the individual biodistribution of the isolated components. However, the anticipated hepatobiliary uptake of different preparations of 99mTc-MAG3 calculated in this way was always lower than that of the experimental value determined directly. Further work is needed to explain the anomaly.     

Adsorption of technetium-99m tetrofosmin and technetium-99m furifosmin on plastic syringes

Mitoxantrone (MIT) is a new anthraquinone anticancer agent. We treated 14 patients with locally advanced breast cancer, 3 of which were inflammatory breast cancers, by pre-operative arterial injection of MIT. The treatment protocol was MIT 12 mg/m2 injected into both the internal mammary and the subclavian arteries with oral administration of 5'-DFUR 1,200 mg/day for 20 days. After 2 courses, all tumors were decreased over 50% in size. Down-staging was obtained in all of 8 cases. Mastectomy could be carried out on all patients, without microscopically residual tumor cells. Preoperative arterial injection of MIT might be the treatment of choice for locally advanced breast cancer to perform down-staging, however the survival benefit has remained equivocal. These preliminary results are encouraging to further studies.     

Extraction and retention of technetium-99m-ECD in human brain: dynamic SPECT and oxygen-15-water PET studies

The kinetic behavior of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in the human brain was investigated in six normal volunteers. METHODS: Dynamic SPECT and a three-compartmental model were used to estimate the rate constants of 99mTc-ECD in normal human brain. Extraction fraction (E), retention fraction (R) and permeability surface area product (PS product) of 99mTc-ECD were calculated using the rate constants. Regional cerebral blood flow (rCBF) was measured by PET with 15O-water. RESULTS: The rate constants in the cerebral cortex were estimated as 0.307 +/- 0.021 for K1 (influx constant), 0.201 +/- 0.047 for k2 (backdiffusion rate constant), 0.547 +/- 0.103 for k3 (lipophilic-to-hydrophilic conversion constant) and 0.0028 +/- 0.0012 for k5 (rate constant from lipophilic compartment to blood) at rCBF of 0.509 +/- 0.055 ml/g/min (mean +/- s.d.). The first-pass extraction, retention fraction and PS product were calculated as 0.608 +/- 0.069, 0.734 +/- 0.047 and 0.477 +/- 0.060, respectively. The first-pass extraction of 99mTc-ECD decreased significantly with increases in rCBF. The retention fraction and PS product of 99mTc-ECD did not show significant changes within the normal range of rCBF. The net extraction of 99mTc-ECD calculated from the static SPECT image obtained from 20 to 40 min was 0.358 +/- 0.039 in the cortex. CONCLUSION: Technetium-99m-ECD has a fairly high brain extraction, and its retention fraction and PS product appear to be independent of rCBF in the healthy human brain.     

Technetium-99m-sestamibi scintimammography for the detection of breast carcinoma: comparison between planar and SPECT imaging

The purpose of our study was to compare the results of planar and SPECT scintimammography for the detection of breast carcinoma. In addition, our goal was to determine whether SPECT reconstructed with filtered backprojection (FBP) or with iterative algorithms (ISA) can improve the sensitivity and specificity of planar scintimammography (SMM). METHODS: One hundred thirteen patients with suspicious physical examinations and/or mammography underwent planar lateral and anterior breast imaging as well as SPECT imaging after injection of 99mTc-sestamibi. We used a blind evaluation, both separately and combined, for planar SMM, ISA-SPECT and FBP-SPECT. Scintigraphic findings were correlated with the final histopathological diagnoses. RESULTS: The sensitivity of planar SMM was 80% with a specificity of 83%. All ISA-SPECT studies were of diagnostic quality, while FBP-SPECT was considered nondiagnostic in 14 that were excluded for statistical calculation. Sensitivity of ISA-SPECT and FBP-SPECT were 71% and 69%, respectively. Specificity was 70% for ISA-SPECT and 66% for FBP-SPECT. Combined planar SMM plus ISA-SPECT sensitivity was 85% (81% for planar SMM plus FBP-SPECT) with a specificity of 72%. Three carcinomas indeterminate on planar SMM were correctly identified by combined planar SMM plus ISA-SPECT. ISA-SPECT and FBP-SPECT provided additional information to planar SMM with respect to localization of sestamibi uptake, tumor extent, improved diagnostic certainty and detection of axillary nodes in 40 and 14 patients, respectively. CONCLUSION: ISA reconstruction is the preferable approach to SPECT data. Combined with planar SMM, ISA-SPECT can improve sensitivity. SPECT is useful in cases of indeterminate and positive planar SMM.     

Role of technetium-99m sestamibi myocardial imaging in the emergency department evaluation of chest pain

The use of technetium-99m sestamibi myocardial imaging is rapidly becoming a state of the art methodology for the emergency department evaluation of patients with chest pain. The following case report represents the first emergency department sestamibi scan ordered at the University of Mississippi Medical Center and is used to discuss the logistics and indications for such tests. A general guideline for ordering sestamibi scans has been developed for use in the emergency department.     

Combined thallium-201 myocardial with technetium-99m-HMPAO brain SPECT: myocardial ischemia induced by acetazolamide in severe coronary artery disease

IgM anti-myelin-associated glycoprotein (anti-MAG)/sulfated glucuronyl paragloboside (SGPG) antibody is found in some patients with chronic polyneuropathy (CP). An antigen-driven process is considered to induce this autoantibody, but the agent has yet to be identified. It has been reported that sera from cytomegalovirus (CMV)-infected patients contained anti-SGPG antibody. To clarify the mechanism of the production of the anti-MAG/SGPG antibody, we investigated CMV DNA in sera from 26 patients with IgM anti-MAG/SGPG antibody-positive CP. Twenty-three (88%) had CMV DNA. The positive frequency was significantly higher than the frequencies in sera from patients with IgM anti-MAG/SGPG-negative CP, the other disease controls, and the normal control subjects. There were no statistical differences in the frequencies of Epstein-Barr virus DNA between anti-MAG/SGPG-positive and anti-MAG/SGPG-negative CP and between anti-MAG/SGPG-positive CP and each disease control. Moreover, no herpes simplex virus 1 DNA was detected in the sera from patients with anti-MAG/SGPG-positive CP. The strong correlation of anti-MAG/SGPG-positive CP with the presence of serum CMV DNA suggests that CMV infection induces the IgM anti-MAG/SGPG antibody.     

False-positive defects in technetium-99m sestamibi myocardial single-photon emission tomography in healthy athletes with left ventricular hypertrophy

Exercise ECG and myocardial single-photon emission tomography (SPET) are fundamental in the non-invasive evaluation of patients suspected of having coronary artery disease (CAD). The purpose of the present study was to investigate the influence of physiological left ventricular hypertrophy (LVH) on myocardial sestamibi SPET in healthy young and old athletes. Eighteen young male elite athletes (ten rowers, five power/weight lifters and three triathletes) and 14 well-trained elderly rowers were studied. All underwent a bicycle test as part of a 2-day sestamibi SPET protocol. Attenuation correction was not performed. The studies were evaluated visually and quantitatively analysed by the CEqual program with its reference files and with a file from a local non-athletic age-matched population. Echocardiographic LVH was an inclusion criterion in the young athletes. Exercise ECG was normal in all subjects. In at least three of the young athletes a reversible defect was observed by visual analysis. On quantitative analysis one-third of the young athletes had "significant" (>10 pixels) defects compared with both the local reference base and the CEqual reference population. Nearly all defects were found in the anterior or inferior wall. The remaining subjects, including all old rowers, had normal SPET findings. Anterior and inferior wall defects are so common in healthy athletes with physiological LVH that the specificity of myocardial SPET, in contrast to exercise ECG, seems to be too low for evaluation of chest pain in this group. The mechanism of anterior and inferior defects may be related to hot spots (papillary muscles?) in the lateral wall. The specificity of SPET is maintained in athletes without LVH.