Clinical applications of 99mTc-sestamibi scintimammography

Mammography is the imaging modality of choice in detection of early, nonpalpable breast cancer. However, scintimammography may prove to be a very useful adjunct to a nondiagnostic or difficult mammography. Future prospective studies will have to be designed so that the specific clinical applications of scintimammography will be well defined. To be clinically relevant, each niche where scintimammography is potentially indicated should be clearly evaluated and incorporated into an algorithm of investigation of breast cancer, taking into consideration the relative advantages and limitations of scintimammography. Special care to obtain high-quality scintimammographic studies is mandatory. Because poor quality studies may be the major drawback, the nuclear medicine community should remind the lesson learned from radiologic mammography. Furthermore, it is also hoped that significant improvement in the scintigraphic equipment and data acquisition will be seen in a very near future to have more widespread clinical diagnostic applications of scintimammography.     

Sensitivity and specificity of planar scintimammography with 99mTc-sestamibi.

PURPOSE: The aim of our prospective study was to determine the diagnostic accuracy of planar breast imaging with 99mTc-MIBI in detecting malignant disease. MATERIAL AND METHODS: Ninety-six consecutive patients with 121 clinically- and/or mammographically-detected breast lesions underwent preoperative planar scintimammography. Ten minutes after injection of 700 MBq 99mTc-MIBI, two lateral prone and one anterior supine projections with an acquisition time of 8 minutes each were obtained. Interpretation of scintimammographic results was made blindly and any focal accumulation of MIBI in the breasts was the criterion for an abnormal scintigram. All lesions were operated on and histologically verified. RESULTS: Histologically, 86 malignant and 35 benign lesions were found in 121 breast lesions. A sensitivity of 83.7% and a specificity of 74.2% for malignancy was achieved at planar scintimammography. CONCLUSION: Scintimammography with 99mTc-MIBI is an imaging modality of modest usefulness in the investigation of breast lesions. The method has a low sensitivity in lesions smaller than 10 mm in diameter, which decreases the clinical use of the method.     

Comparison of planar and SPECT scintimammography with 99mTc-sestamibi in the diagnosis of breast carcinoma

PURPOSE: To compare results of planar and SPECT breast imaging with 99mTc-MIBI in detecting primary breast cancer. MATERIAL AND METHODS: Twenty-six consecutive patients with 34 suspected breast lesions underwent both planar and SPECT scintimammography. Ten minutes after injection of 700 MBq 99mTc-MIBI, 2 prone lateral projections were obtained, followed by a supine anterior projection. Forty minutes after injection, a SPECT study was done. All lesions were operated upon and verified with histopathology. RESULTS: A sensitivity of 85% and specificity of 88% of planar scintimammography in diagnosis of primary breast lesions were achieved. The corresponding values for SPECT were 61% and 64%. CONCLUSION: The diagnostic accuracy of planar scintimammography was not improved by using SPECT imaging.     

Double-phase 99mTc-sestamibi scintimammography and trans-scan in diagnosing breast cancer.

The goal of our study was to assess the value of both scintimammography with 99mTc-sestamibi (SMM) and trans-scan (T-scan) in detecting breast cancer. METHODS: A total of 121 women were evaluated by palpation, mammography, SMM and T-scan. SMM was performed in the prone, breast dependent position. Immediate and delayed views (double-phase) were obtained. T-scan is a new breast imaging method that maps noninvasively the distribution of tissue electrical impedance and capacitance. RESULTS: SMM had 88.9% sensitivity, 88.4% specificity and 88.4% accuracy in detecting breast cancer. SMM had 100% sensitivity in detecting breast tumors >1 cm and only 66% sensitivity in detecting tumors <1 cm. T-scan had 72.2% sensitivity and 67% specificity in detecting breast cancer. It detected one more breast cancer than SMM, at the expense of 27 additional false-positive results. CONCLUSION: Double-phase SMM was sensitive and specific in detecting breast cancer. This method may reduce the rate of negative breast biopsies in tumors >1 cm. T-scan was only moderately accurate in detecting breast cancer. Its addition to SMM did not improve significantly the rate of breast cancer detection. However, because of its complete noninvasiveness, large-scale applicability and low cost, T-scan deserves further refining.     

Comparison of 99mTc-sestamibi scintimammography and dynamic MR imaging as adjuncts to mammography in the diagnosis of breast cancer

PURPOSE: To compare the diagnostic accuracy of planar 99mTc-sestamibi scintimammography with dynamic contrast-enhanced MRI (CE-MRI) on the basis of histopathologic results, and to determine the clinical value of these methods as adjuncts to mammography. MATERIAL AND METHODS: A total of 90 consecutive women with 111 histopathologically verified breast lesions were enrolled in the study. Patients underwent scintimammography and CE-MRI in addition to mammography. Each finding was classified on a BI-RADS-like five-point rating scale describing the degree of suspicion for malignancy, and all findings were correlated with the histopathological results. RESULTS: The overall sensitivity/specificity/accuracy was 85%/59%/78% for mammography, 94%/47%/80% for CE-MRI, and 82%/75%/80% for scintimammography, respectively. CE-MRI showed higher sensitivity (p = 0.008), but its specificity was lower than scintimammography (p = 0.049). Using ROC analysis, significant improvement ( p = 0.034) was found between mammography and the combination of mammography + CE-MRI, while mammography + scintigraphy showed no higher diagnostic accuracy than mammography alone. CONCLUSION: If high sensitivity and spatial resolution are needed, CE-MRI is to be preferred in clinical practice as an adjunct to mammography, rather than scintigraphy.     

Comparative value of 99mTc-sestamibi scintimammography and sonography in the diagnostic workup of breast masses

OBJECTIVE: This study was conducted to assess the relative roles of 99mTc-sestamibi scintimammography and sonography in the evaluation of breast lesions that are indeterminate or suspicious on mammography or clinical examination. SUBJECTS AND METHODS: Twenty-five patients with 33 biopsy-proven breast lesions underwent both scintimammography and sonography. Lesions were categorized as benign or requiring biopsy on the basis of the absence or presence of a focus of increased activity on scintimammography and the shape, orientation, and echogenicity of the lesion on sonography. RESULTS: Sensitivity and specificity in detecting breast cancer were 92% and 95%, respectively, for scintimammography and 100% and 48%, respectively, for sonography. The higher specificity of scintimammography was statistically significant (p < 0.01). CONCLUSION: Although the overall accuracy of 99mTc-sestamibi scintimammography in the diagnosis of breast cancer was high, it has several disadvantages in comparison with sonography. Scintimammography has a slightly higher false-negative rate for breast cancer, is unable to reveal cysts, is more expensive, takes longer to perform, and involves ionizing radiation. For these reasons, scintimammography with 99mTc-sestamibi is unlikely to either replace sonography or be frequently used in addition to sonography.     

Contribution of 99mTc-anti-carcinoembryonic antigen antibody and 99mTc-sestamibi scintimammography in the evaluation of high risk palpable breast lesions

Mammography is the screening test of choice for breast cancer. Its low specificity leads to a large number of unnecessary biopsies. Scintimammography, with either Tc-sestamibi (MIBI) or Tc-anti-carcinoembryonic antigen (CEA) Fab', has been proposed as a non-invasive test to lower the high false positive rate of mammography in certain patients. The two agents have not been compared, nor has their combined application been evaluated. We performed a prospective, non-randomized, open-label, single-centre study of 32 women with clinically and mammographically suspected breast cancer [Breast Imaging Reporting and Data System (BI-RADS, American College of Radiology) 4 or 5]. All patients underwent Tc-MIBI and Tc-anti-CEA Fab' scintimammography, and the results were correlated with histopathology. Overall, the accuracies for MIBI and CEA scans were 90.3% (28/31) and 77.4% (24/31), respectively. The probability of disease after mammography was 0.939+/-0.081 (95% confidence interval, CI). The post-mammography probabilities after positive MIBI or CEA scan were 0.965 and 0.960, respectively, and after negative MIBI or CEA scan 0.750 and 0.875, respectively. None of the above differences is significant. The post-test probability when both scans were positive (irrespective of which was performed first) was 0.977. It can be concluded that there are indications that scintimammography with Tc-MIBI is superior to that with Tc-anti-CEA Fab' when these tests are used as screening tests for breast cancer. However, mammography remains the screening test of choice for highly suspicious clinically palpable breast lesions. In this group of patients, the application of scintimammography with either Tc-MIBI or Tc-anti-CEA Fab' (alone or in combination) offers no additional advantage.     

18F-FDG PET and 99mTc-sestamibi scintimammography for monitoring breast cancer response to neoadjuvant chemotherapy: a comparative study

Presurgical neoadjuvant chemotherapy has shown promise in the treatment of locally advanced breast carcinoma (LABC). Response assessment by clinical examination and mammography is difficult. This study evaluated and compared fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) and technetium-99m sestamibi scintimammography (SMM) as potential methods for the early assessment of tumour response to neoadjuvant chemotherapy in patients with LABC. Seven patients underwent PET and SMM [planar and single-photon emission tomography (SPET)] before beginning chemotherapy, after the first and second cycles of chemotherapy and after completing chemotherapy prior to surgery. PET and SMM results were evaluated visually and semi-quantitatively by calculating standardised uptake values (SUV) and tumour/lung ratios in the initial and subsequent studies. The findings were correlated with the initial clinical and mammographic findings and the final histopathological diagnoses. There was a highly significant correlation between SUV_mean, SUV_max and the tumour/lung ratio determined with SMM-SPET in the studies performed before and during neoadjuvant chemotherapy. All three patients with complete remission showed decreasing FDG and sestamibi uptake as early as 8 days after therapy. In the presurgical study, increased sestamibi and FDG uptake was no longer evident. Three patients had partial remission with clearly reduced but persisting focal FDG and sestamibi uptake after neoadjuvant therapy. One patient who did not respond to therapy had unchanged intense tracer uptake during chemotherapy that was evident with both techniques. An early decline in glucose metabolism or sestamibi uptake 8 days after beginning therapy did not necessarily predict complete tumour remission in the further course of chemotherapy. On the other hand, increased tracer uptake after the first cycle did not exclude a partial tumour response. After the second chemotherapeutic cycle both techniques were able to distinguish between complete and partial/no response. There was a good correlation between preoperative FDG and sestamibi uptake and the histopathologically determined tumour size. However, small residual invasive tumours in patients with clinically complete remission could not be visualised with either technique. The preliminary data demonstrate that sestamibi SMM is as useful as FDG-PET for the monitoring of tumour response to neoadjuvant chemotherapy.     

18F-FDG PET and 99mTc-sestamibi scintimammography for monitoring breast cancer response to neoadjuvant chemotherapy: a comparative study.

Presurgical neoadjuvant chemotherapy has shown promise in the treatment of locally advanced breast carcinoma (LABC). Response assessment by clinical examination and mammography is difficult. This study evaluated and compared fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and technetium-99m sestamibi scintimammography (SMM) as potential methods for the early assessment of tumour response to neoadjuvant chemotherapy in patients with LABC. Seven patients underwent PET and SMM [planar and single-photon emission tomography (SPET)] before beginning chemotherapy, after the first and second cycles of chemotherapy and after completing chemotherapy prior to surgery. PET and SMM results were evaluated visually and semi-quantitatively by calculating standardised uptake values (SUV) and tumour/lung ratios in the initial and subsequent studies. The findings were correlated with the initial clinical and mammographic findings and the final histopathological diagnoses. There was a highly significant correlation between SUVmean, SUVmax and the tumour/lung ratio determined with SMM-SPET in the studies performed before and during neoadjuvant chemotherapy. All three patients with complete remission showed decreasing FDG and sestamibi uptake as early as 8 days after therapy. In the presurgical study, increased sestamibi and FDG uptake was no longer evident. Three patients had partial remission with clearly reduced but persisting focal FDG and sestamibi uptake after neoadjuvant therapy. One patient who did not respond to therapy had unchanged intense tracer uptake during chemotherapy that was evident with both techniques. An early decline in glucose metabolism or sestamibi uptake 8 days after beginning therapy did not necessarily predict complete tumour remission in the further course of chemotherapy. On the other hand, increased tracer uptake after the first cycle did not exclude a partial tumour response. After the second chemotherapeutic cycle both techniques were able to distinguish between complete and partial/no response. There was a good correlation between preoperative FDG and sestamibi uptake and the histopathologically determined tumour size. However, small residual invasive tumours in patients with clinically complete remission could not be visualised with either technique. The preliminary data demonstrate that sestamibi SMM is as useful as FDG-PET for the monitoring of tumour response to neoadjuvant chemotherapy.     

The role of scintimammography with 99mTc-sestamibi as a complementary diagnostic technique in the detection of breast cancer

Purpose: To prospectively determine the clinical value of scintimammography (Sc) with ^99mTc-sestamibi as a complementary method to triple diagnosis (TD) in detecting malignant disease of the breast.Material and Methods: Ninety-six patients with 119 clinically or mammographically detected breast lesions underwent TD procedures, including clinical examination, mammography and fine-needle aspiration cytology. Prone planar Sc with ^99mTc-sestamibi was performed in all 96 patients. Five groups were defined for diagnosis: 1=normal; 2=benign; 3=probably benign; 4=highly suspect of malignancy; and 5=malignant. All lesions were histopathologically examined. The results of each method per se and the combination of TD with Sc (TD+Sc) were analyzed.Results: Histopathology of the 119 surgically excised breast lesions found 83 malignant and 36 benign lesions. TD missed 6 of 83 carcinomas, resulting in a sensitivity of 92.7%. Sc alone showed sensitivity of 85.5%. The combination TD+Sc missed 1 of 83 carcinomas, and thus had a sensitivity of 98.7%. In mammographically dense breasts both TD and Sc detected 16 of 18 carcinomas, while the combination TD+Sc led to detection of all 18 carcinomas.Conclusion: Adding Sc to TD increases the sensitivity for detection of breast carcinomas. Sc with ^99mTc-sestamibi is recommended as a complimentary method to TD in selected cases such as mammographically dense breasts.     

Differences between 99mTc-sestamibi and 99mTc-tetrofosmin uptake in thyroid and salivary glands: comparison with 99mTc-pertechnetate in 86 subjects

Tc-tetrofosmin seems to show a prolonged thyroid retention when compared with Tc-sestamibi; this may explain its poorer performance in the dual-phase parathyroid scintigraphy. In order to verify objectively whether and to what extent Tc-sestamibi and Tc-tetrofosmin uptake and retention differ in the thyroid gland, we performed a head-to-head comparison between the tracers in 86 euthyroid subjects enrolled in five centres. Data were compared with those of Tc-pertechnetate obtained from the same subjects. For comparison purposes, quantitative data from the salivary glands were also obtained. Tc-sestamibi showed a higher early thyroid uptake (2.26+/-0.52 vs. 2.01+/-0.49, respectively; P<0.002) and a lower retention (1.4+/-0.37 vs. 1.65+/-0.58, respectively; P<0.002) when compared with Tc-tetrofosmin. This finding provides an objective basis for the poorer results of Tc-tetrofosmin in dual-phase parathyroid scintigraphy. Delayed Tc-tetrofosmin salivary gland uptake was unexpectedly high and approached the Tc-pertechnetate value (2.29+/-0.56 vs. 2.46+/-0.75, respectively; P =not significant). This finding should be kept in mind in order to avoid interpretation pitfalls in thyroid and parathyroid imaging with Tc-tetrofosmin, as well as in other oncological imaging of the neck region. This study definitely establishes that Tc-tetrofosmin and Tc-sestamibi are not twin but rather sibling tracers.     

Scintigraphic findings on99mTc-MDP,99mTc-sestamibi and99mTc-HMPAO images in Gaucher's disease

Gaucher's disease is an autosomal recessive lysosomal storage disease characterized by the specific deficiency of glucocerebrosidase that leads to accumulation of insoluble glucocerebroside in the reticuloendothelial system, particularly the bone marrow, liver, spleen and lymph nodes. Direct scintigraphic visualization of lipid deposits in Gaucher's disease has recently been described, based on the use of the lipid-soluble xenon-133. We report here on the use of the lipophilic cat-ionic complex technetium-99m sestamibi (^99mTc-MIBI), employed as an indicator of increased cellular density and metabolic activity, to evaluate Gaucher cell infiltrates in the bone marrow;^99mTc-hexametazime (^99mTc-HMPAO) was also employed, as a pure indicator of lipidic infiltration in the bone marrow. A 67-year-old patient with known type 1 Gaucher's disease presented with a painful left hip and knee and difficulty in gait subsequent to traumatic fracture of the left femoral neck that had required implant of a fixation screw-plaque. Bone scan with^99mTc-methylene diphosphonate revealed reduced uptake at the distal metaphyseal-epiphyseal femoral region. In addition, whole-body maps and spot-view acquisitions of the thighs and legs were recorded at both 30 min and 2.5 h after the injection of^99mTc-MIBI: the scintigraphic pattern clearly showed increased uptake at several sites involved by Gaucher deposits in the bone marrow (both knees, with variable intensity in different areas), matching the bone changes detected by conventional x-ray. The target to non-target ratios slowly decreased with time, from an average value of 2.25 in the early scan to an average value of 2 in the delayed scan. The lipid-soluble agent^99mTc-HMPAO exhibited a superimposable scintigraphic pattern of accumulation at the involved sites, though with lower target to non-target ratios (1.27–1.48). The results obtained in this patient suggest a potential role of^99mTc-MIBI in the scintigraphic evaluation of Gaucher's lipid deposits in the bone marrow. If the results are confirmed in other patients, this radiopharmaceutical would offer clear advantages over¹³³Xe because of its wider availability and greater practicality (i.v. administration of^99mTc-MIBI versus inhalation of¹³³Xe, and use of a single gamma camera instead of two as with¹³³Xe).     

New bone-seeking agent: Animal study of Tc-99m-incadronate

OBJECTIVE: Disodium cycloheptylaminomethylenediphosphonate monohydrate (incadronate disodium) is a third-generation bisphosphonate compound which potently inhibits bone resorption, and a highly effective drug in the treatment of metastatic bone disease. We first labeled incadronate disodium with 99mTc, and examined its biodistribution and bone uptake after intravenous injection in rats to assess its potential for clinical use as a bone-seeking agent for judgment of the therapeutic effect of incadronate on bone metastases. Bone scan with 99mTc-labeled incadronate (99mTc-incadronate) may yield important information prior to the use of incadronate for treatment of bone metastases. METHODS: Synthesis of 99mTc-incadronate was carried out by reduction of 99mTc-pertechnetate in the presence of SnCl2 and N2 gas. Normal rats were injected with 18.5 MBq (0.5 mCi) 99mTc-incadronate in a volume of 0.1 ml intravenously and then sacrificed at 15 min, 30 min, 1 h or 2 h (six rats at each time point) after injection. Samples of muscle, stomach, small intestine, kidney, liver and bone (femur) were taken and weighed. In addition, a 1-ml sample of blood was drawn from the heart, and urine was taken from the urinary bladder immediately after sacrifice. Samples were measured for radioactivity and expressed as percent uptake of injected dose per gram or per milliliter (% ID/g or ml). Bone-to-blood and bone-to-muscle uptake ratios were determined from the % ID/g or ml values for these organs. RESULTS: The greatest accumulation of 99mTc-incadronate was found in bone. Radioactivity in bone was as high as 3.22 +/- 0.68% ID/g at 2 hours after injection. Scintigraphic images of 99mTc-incadronate in normal rats revealed highly selective skeletal uptake. CONCLUSION: 99mTc-incadronate exhibited high uptake in bone, and relatively low uptake in soft tissue, suggesting that it may be useful as a bone-seeking agent for judgment of the therapeutic effect of incadronate on bone metastases, by determining the degree of its accumulation in metastatic bone lesions.     

99mTc-exametazime as a breast tumor-seeking agent: comparison with 99mTc-sestamibi.

(99m)Tc-sestamibi is commonly used for mammoscintigraphy. Occasional uptake of (99m)Tc-exametazime in various tumors has been described. In this study, an intraindividual comparison of these 2 radiopharmaceuticals for mammoscintigraphy was made. METHODS: A kinetic study (30 min) in the lateral prone view of 20 breast tumors (> or =1 cm) in 20 women was conducted with (99m)Tc-exametazime. Thereafter, 21 breast tumors (> or =1 cm) in 21 women were examined with both agents (2 patients were included in both groups) under identical conditions (interval, 2-7 d). In the latter group, the tumor-to-background breast activity ratio and the tumor uptake normalized to the administered activity (cps/MBq) at 10 min after injection were calculated and compared for both agents. RESULTS: All tumors (43 tumors in 39 patients) were visualized with (99m)Tc-exametazime. There was also one instance of false-positive uptake using this agent. The uptake phase lasted approximately 10 min. Thereafter, the activity was practically stable. (99m)Tc-Sestamibi failed to depict 4 tumors. On the group level, the tracers did not differ in tumor-to-background activity ratio or normalized tumor uptake. Intraindividual agreement in tumor-to-background ratios between the tracers was moderate (intraclass correlation coefficient = 0.49). CONCLUSION: Uptake of (99m)Tc-exametazime in breast tumors > or = 1 cm seems to be comparable with that of (99m)Tc-sestamibi at a group level. The specificity is unknown. There is a restricted intraindividual agreement between the tracers, confirming different uptake mechanisms. This may open up possibilities for assessing different tumor characteristics in vivo, especially since the uptake of both agents is based on mechanisms believed to be involved in resistance to antineoplastic drugs.     

Efficacy of 99mTc-sestamibi SPECT/CT for minimally invasive parathyroidectomy: comparative study with 99mTc-sestamibi scintigraphy, SPECT, US and CT

Purpose

We evaluated the efficacy of ^99mTc-sestamibi SPECT/CT for planning minimally invasive parathyroidectomy (MIP), comparing with dual phase ^99mTc-sestamibi scintigraphy, ^99mTc-sestamibi SPECT and conventional imaging (US and CT).

Methods

Thirty-one patients (M:F?=?10:21, range 35?C78?years old) who showed high serum parathyroid hormone (intact PTH) level were included. ^99mTc-sestamibi scintigraphy was performed 15 and 150?min after injection of ^99mTc-sestamibi (555?MBq), and ^99mTc-sestamibi SPECT/CT was obtained just after the delayed scan. Comparison study between imaging modalities was done by patient-based and lesion location-based analysis. The location of the lesion was confirmed by the operative finding. An operation was performed in 24 patients. Seven patients had normal ^99mTc-sestamibi SPECT/CT, and followed for more than 6?months after SPECT/CT.

Results

Among 24 patients, parathyroid adenoma was detected in 19 patients and the other 5 had parathyroid hyperplasia (total 35 lesions). ^99mTc-sestamibi scintigraphy detected abnormal uptake in 15 patients with 24 lesions. Conventional imaging identified abnormal findings in 17 patients with 27 lesions. SPECT detected abnormal findings in 18 patients with 27 lesions. SPECT/CT identified abnormal findings in 24 patients with 35 lesions. SPECT/CT demonstrated 100?% sensitivity in a patient-based analysis. SPECT/CT exhibited significantly better sensitivity than ^99mTc-sestamibi scintigraphy, SPECT and conventional imaging (p?<?0.05). All lesion location was correctly identified to perform MIP. The final clinical diagnosis of 7 normal SPECT/CT patients was secondary hyperparathyroidism on 6?months follow-up.

Conclusions

We correctly identified the precise location of parathyroid adenomas or hyperplasia by ^99mTc-sestamibi SPECT/CT which was helpful to perform MIP.