99mTc-Radiolabeled TPGS Nanomicelles Outperform 99mTc-Sestamibi as Breast Cancer Imaging Agent.

D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) is a Food and Drug Administration (FDA) approved biomaterial that can form nanosized micelles in aqueous solution. TPGS micelles stand as an interesting system to perform drug delivery as they can carry lipophilic drugs and overcome P glycoprotein efflux as well. Therefore, TPGS micelles combined with other copolymers have been reported in many cancer research studies as a carrier for therapeutic drugs. Their ability to reach tumoral tissue can also be exploited to develop imaging agents with diagnostic application. A radiolabeling method with 99mTc for TPGS nanosized micelles and their biodistribution in a healthy animal model as well as their pharmacokinetics and radiolabeling stability in vivo was previously reported. The aim of this work was to evaluate the performance of this radioactive probe as a diagnostic imaging agent compared to routinely available SPECT radiopharmaceutical, 99mTc-sestamibi. A small field of view gamma camera was used for scintigraphy studies using radiolabeled TPGS micelles in two animal models of breast cancer: syngeneic 4T1 murine cell line (injected in BALB/c mice) and chemically NMU-induced (Sprague-Dawley rats). Ex vivo radioactivity accumulation in organs of interest was measured by a solid scintillation counter, and a semiquantitative analysis was performed over acquired images as well. Results showed an absence of tumoral visualization in 4T1 model for both radioactive probes by gamma camera imaging. On the contrary, NMU-induced tumors had a clear tumor visualization by scintigraphy. A higher tumor/background ratio and more homogeneous uptake were found for radiolabeled TPGS micelles compared to 99mTc-sestamibi. In conclusion, 99mTc-radiolabeled TPGS micelles might be a potential SPECT imaging probe for diagnostic purposes.

Heart and systemic effects of statin pretreatment in a rat model of abdominal sepsis. Assessment by Tc99m-sestamibi biodistribition.

PURPOSE: To evaluate the heart and the Tc-99m-sestamibi biodistribution after statin pretreatment in a rat model of abdominal sepsis. METHODS: Twenty-four Wistar rats were randomly distributed into four groups (n=6 per group): 1) sepsis with simvastatin treatment, 2) sepsis with vehicle, 3) sham control with simvastatin and 4) sham control with vehicle. 24 hours after cecal ligation and puncture rats received 1.0MBq of Tc-99m-sestamibi i.v. 30min after, animals were euthanized for ex-vivo tissue counting and myocardium histological analysis. RESULTS: Myocardial histologic alterations were not detected 24 hours post-sepsis. There was significantly increased cardiac Tc-99m-sestamibi activity in the sepsis group with simvastatin treatment (1.9±0.3%ID/g, p<0.001) in comparison to the sepsis group+vehicle (1.0±0.2%ID/g), control sham group+ simvastatin (1.2±0.3%ID/g) and control sham group (1.3±0.2%ID/g). Significant Tc-99m-sestamibi activity in liver, kidney and lungs was also detected in the sepsis group treated with simvastatinin comparison to the other groups. CONCLUSIONS: Statin treatment altered the biodistribution of Tc-99m-sestamibi with increased cardiac and solid organ activity in rats with abdominal sepsis, while no impact on controls. Increased myocardial tracer activity may be a result of a possible protection effect due to increased tissue perfusion mediated by statins.

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.

99mTechnetium-SESTAMIBI uptake in malignant lymphomas. Correlation with chemotherapy response.

BACKGROUND: The rationale of the present study is based on the property of technetium-SESTAMIBI to enter malignant and other highly metabolic cells, and then to be pumped out of them by the multidrug-resistant (MDR) system, strongly depending on the expression of the MDR-1 gene encoded P-glycoprotein (Pgp-170). METHODS AND RESULTS: Forty-one patients with malignant lymphoma were studied before chemotherapy. Images were taken 30 min (early) and 180 min (late) after intravenous injection of (99m)Tc-MIBI, and then visually interpreted. They were correlated with clinical response defined as chemosensitive (ChS) when a >6 month remission was attained, and chemoresistant (ChR) to any other response. Of 41 patients, 27 had an early positive uptake, 18 (67%) were ChS, and 9 (33%) ChR. Of these 27 patients, 19 also had late positive scans; 15 (79%) were ChS, and only 4 were ChR (p = 0.037). Conversely, 10 of 14 remaining patients with negative early scans were ChR. Eight patients had an early positive study; however, the late retention of (99m)Tc-MIBI was negative and the relationship to chemotherapy response was not conclusive. A breakdown of data was made according to histology. Patients with low grade lymphoma had the strongest correlation between (99m)Tc-MIBI uptake and chemosensitivity. Patients with high grade lymphoma had only a trend, and patients with Hodgkin's disease had an indefinable correlation. CONCLUSIONS: This study takes advantage of the relationship between the ability to uptake and retain (99m)Tc-MIBI, a Pgp-170 substrate, by lymphomatous tumors. This attribute, combined with other clinical data, could help to select tailored treatments for patients that are likely to be chemoresistant before treatment.

MIBI scintigraphy, indicators of cell proliferation and histology of parathyroid glands in uraemic patients.

BACKGROUND: Although scintigraphy with (99m)Tc-sestamibi (MIBI) has been used to localize parathyroid glands prior to surgery for hyperparathyroidism, using it to evaluate parathyroid function remains controversial. The purpose of this study was to evaluate the possible association of MIBI uptake with gland weight, histological pattern and proliferative activity of parathyroid cells. METHODS: We studied 18 patients with secondary hyperparathyroidism (SHP); mean age 38+/-3 years, 55% female, mean time on haemodialysis 7.7+/-0.9 years. All patients had parathyroidectomy (PTx). The weights of the removed glands were estimated, and parathyroid hyperplasia was classified as diffuse (n = 28) or nodular (n = 29). The expression of proliferative cell nuclear antigen (PCNA) was evaluated by immunohistochemistry. Before PTx, all patients underwent MIBI evaluation and were categorized using a 0-3 uptake scoring system. Low uptake (scores of 0 and 1) was seen in 39 glands and high uptake (scores of 2 and 3) in 18. RESULTS: Estimated gland weights, percentage of nodular hyperplasia and PCNA expression were greater in glands with high MIBI scores than in those with low scores (P<0.01). In glands with nodular hyperplasia, PCNA expression was higher (318+/-66 cells/mm2) than in those with diffuse hyperplasia (104+/-16 cells/mm2; P<0.001). CONCLUSIONS: High MIBI scores were associated with high estimated gland weight, degree of cell proliferation and presence of nodular hyperplasia. MIBI scintigraphy is useful in clinical practice for localizing parathyroid glands, and it could guide the management of SHP by indicating the degree of its severity.

99mTc-sestamibi thyroid uptake in euthyroid individuals and in patients with autoimmune thyroid disease.

PURPOSE: We investigated the biokinetics of (99m)Tc-sestamibi in the thyroid of euthyroid volunteers (EVs) and in patients with autoimmune thyroid diseases and determined the best time interval between (99m)Tc-sestamibi injection and calculation of uptake. METHODS: Forty EVs, 30 patients with Graves' disease (GD), 15 patients with atrophic Hashimoto's thyroiditis (AHT) and 15 patients with hypertrophic Hashimoto's thyroiditis (HHT) underwent (99m)Tc-sestamibi thyroid scintigraphy. Dynamic images were acquired for 20 min, and static images were obtained 20 min, 60 min and 120 min post injection. Five-, 20-, 60- and 120-min uptake, time to maximal uptake (T(max)) and T(1/2) of tracer clearance were calculated. Thyroid hormones and antibodies were measured. (99m)Tc-pertechnetate uptake was investigated in GD patients. RESULTS: T(max) was approximately 5 min in all four groups. The mean T(1/2) value for EVs was similar to the GD value and lower than the HHT and AHT values. The mean (+/-SD) 5-min uptake was 0.13% (+/-0.05%) for EVs. The 5-min uptake in GD was higher than that in EVs(P<0.001) and correlated with free thyroxine (r=0.54) and with (99m)Tc-pertechnetate uptake (r=0.68). Uptake in HHT was higher than that in AHT (P=0.0003) and EVs (P=0.002). Uptake in AHT was lower than uptake in EVs (P=0.0001). CONCLUSION: Five minutes is the optimal time interval between (99m)Tc-sestamibi injection and calculation of thyroid uptake. Five-minute uptake differentiates euthyroid individuals from GD patients. There is a high correlation between (99m)Tc-sestamibi and (99m)Tc-pertechnetate uptake in GD. The reduced (99m)Tc-sestamibi uptake in AHT patients is probably due to glandular destruction and fibrosis. Inflammatory infiltrate and high mitochondrial density in thyrocytes possibly explain the increased uptake in GD and HHT.

Gamma probe-assisted brain tumor microsurgical resection: a new technique.

OBJECTIVES: The pioneering performance of gamma probe-assisted surgery (GPAS) for brain tumors, aiming not only an improvement of tumor detection, but mainly assurance of its complete removal and the study of the usual distribution of the 99mTc-MIBI in the brain SPECT of normal individuals. METHOD: Patient's informed consent and demonstration of the tumor by the preoperative MIBI SPECT were the inclusion criteria adopted for GPAS, which was performed in one patient with a right parietal lobe metastatic tumor. The radiotracer (99mTc-MIBI) was injected in a peripheral vein 5 hours before the operation. A tumor to-normal tissue count ratio equal to or greater than 2/1 was considered indicative of tumor. MIBI SPECT was performed in five normal individuals in a pilot study. RESULTS: The gamma probe greatly facilitated intraoperative tumor detection (tumor to-normal brain count ratio was 5/1) and indicated a small piece of residual tumor after what was thought to be a complete tumor removal, allowing its resection, which, otherwise, would have been left behind. Postoperative CT confirmed complete tumor resection. The MIBI SPECT in normal individuals showed an increased uptake by the hypophisis, choroid plexus, skull, scalp and salivary glands and absence of uptake by the normal brain tissue. There were no complications. CONCLUSION: GPAS proved to be, in this single case, a safe and reliable technique to improve brain tumor detection and to confirm the presence or absence of residual tumor.

Thyroid imaging with Tc-99m MIBI in patients with solitary cold single nodules on pertechnetate imaging.

Thyroid imaging was performed in 30 patients with the standard pertechnetate technique, as well as with Tc-99m MIBI using a double-phase acquisition protocol. All patients had normal thyroid function confirmed by hormone measurements and cold solitary thyroid nodules, which were evaluated by pertechnetate scanning. Tc-99m MIBI scans were reported as showing cold (N = 14), warm (N = 7), or hot (N = 9) nodules. Nodule classification was made according to fine needle aspiration biopsy findings in 20 patients. The remaining 10 proceeded to surgery and had histopathologic confirmation of their lesions. Although all cold nodules with Tc-99m MIBI were cystic, six of the warm nodules were benign lesions. No histologically proven benign nodule was hot with Tc-99m MIBI. Of the hot nodules, seven were suspicious for follicular carcinoma with fine needle aspiration biopsy (N = 3), or had histologically proven papillary carcinoma (N = 4). Delayed images in five of seven of these lesions showed nodular retention of the radiopharmaceutical. In conclusion, double-phase Tc-99m MIBI scanning of the thyroid gland could be helpful in the preoperative assessment of patients with cold solitary thyroid nodules in order to evaluate the malignancy probability of these lesions.