Influence of the heterogeneity of P-glycoprotein expression on technetium-99m-MIBI uptake in breast cancer.

UNLABELLED: We prospectively studied a total of 30 patients with breast cancer to evaluate the relationship between the degree of accumulation of 99mTc-sestamibi (MIBI) and the heterogeneity of p-glycoprotein expression in tumor tissues. METHODS: Twenty patients during initial presentation and 10 patients during post-therapy evaluation underwent contemporaneous 99mTc-MIBI imaging and surgery or biopsy. Immunohistochemical studies were performed on multiple nonconsecutive sections of the same tumor using a p-glycoprotein-specific monoclonal antibody, JSB-1. Tumor-to-background (T/B) ratios were correlated with the level and heterogeneity of p-glycoprotein expression determined by immunohistochemical studies. RESULTS: The T/B ratios were lower for those tumors with strong p-glycoprotein expression (Group 1) than those with strong-to-weak expression (Group 2) or those with weak-to-no expression (Group 3) (1.32 +/- 0.19 and 1.85 +/- 0.56 and 2.86 +/- 1.06, respectively). There was statistically significant difference in T/B ratios between all 3 groups (p < 0.005). Although T/B ratios for Group 1 and Group 3 were clearly distinct from one another with no overlapping values, the values for Group 2 overlapped with those of Group 1 and Group 3. When we evaluated the entire patient group with excluding those with strong-to-weak expression, although the p value remained the same (p < 0.001), we obtained a stronger correlation between T/B ratios and p-glycoprotein expression (r = 0.808 versus 0.735). CONCLUSION: Due to the heterogeneous expression of p-glycoprotein, both immunohistochemistry and 99mTc-MIBI scintigraphy may yield confounding results by contrasting with one another if the presence or absence of p-glycoprotein is not extensively explored. Although our data confirmed that 99mTc-MIBI imaging is useful in the determination of the presence of multidrug resistance in patients with breast cancer, the issue of heterogeneous expression of the antigen should be further investigated when unexpected results are obtained.

Association of tumor washout rates and accumulation of technetium-99m-MIBI with expression of P-glycoprotein in lung cancer.

UNLABELLED: In a prospective study, we correlated the washout rates of 99mTc-sestamibi (MIBI) and the degree of MIBI accumulation with the expression of P-glycoprotein (Pgp) in tumor tissues in a total of 46 patients with lung cancer. METHODS: All patients underwent early (30 min) and delayed (3 hr) MIBI imaging and bronchoscopic biopsy before initiation of chemo- or radiotherapy. The interval between biopsy and imaging varied between 2 and 10 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 Pgp. Normal tissue and tumor washout rates and tumor-to-background ratios were correlated with the level of Pgp expression. RESULTS: There was an inverse correlation between tumor-to-background ratios and the density of Pgp (p = 0.001), whereas there was no appreciable correlation between tumor washout rates of MIBI and the level of Pgp expression (p = 0.414). CONCLUSION: The current data strongly suggest that, although the reduced ability for the tumors to accumulate MIBI correlates well with the increased levels of Pgp expression, tumor washout rates of MIBI do not correlate with the density of Pgp in tumor tissues. Our results also warrant additional research for correlating immunohistological and imaging findings with messenger RNA levels determined by polymerase chain reaction and flow cytometry.

Pre- and post-therapy thallium-201 and technetium-99m-sestamibi SPECT in nasopharyngeal carcinoma.

UNLABELLED: We prospectively studied the diagnostic potential of 201Tl and 99mTc-sestamibi (MIBI) SPECT for evaluating the extent of primary disease and differentiating residual/recurrent disease from post-therapy changes in patients with nasopharyngeal carcinoma (NPC). METHODS: Fifty patients (20 initial presentation, 30 post-therapy evaluation) underwent 201Tl and MIBI imaging. The findings were correlated with CT/MRI results. Tumor-to-background ratios were obtained. Biopsy confirmation (14 patients) and/or 6-12 mo clinical follow-up data (16 patients) were available in the post-therapy group. RESULTS: All primary disease sites were accurately detected by both imaging studies in the pretherapy group. However, MIBI-SPECT was superior to 201Tl SPECT (p = 0.0057) in detecting regional metastases (sensitivities of 95% versus 68%). In the post-therapy group, MIBI and 201Tl imaging were true-positive in 14 of 16 patients with proven residual/recurrent. In 17 patients who had no evidence of residual/recurrent tumor. CT/MRI was false-positive in 13 when MIBI and 201Tl imaging were true-negative in 10 and false positive in 3. MIBI, 201Tl and CT/MRI had sensitivities of 87.5%, 87.5%, 100%, specificities of 82.4%, 76.5%, 23.5% and accuracies of 85%, 82%, 61%, respectively. Tumor-to-background ratios were < or = 1.5 in all false-positive cases except one. CONCLUSION: MIBI-SPECT proves more accurate than 201Tl SPECT in detecting regional metastases at initial presentation. MIBI and 201Tl imaging have higher specificity and accuracy than CT/MRI and MIBI-SPECT is slightly more specific than 201Tl SPECT in differentiating residual/ recurrent disease from post-therapy changes in patients with NPC.

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

UNLABELLED: 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.

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

UNLABELLED: 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.

The utility of fractional wash-out slope values following intravenous 133Xe.

The regional clearance of 133Xe from the lungs after intravenous administration as well as following rebreathing was assessed in 7 normals and 18 patients with various lung disorders. Each lung was divided into three zones as upper, middle and lower. Regional ventilation (V) and regional perfusion (P) were determined using the area under the first peak at the beginning of the ventilation study and the area under the peak after intravenous administration, respectively. Slopes were calculated using the first exponential of the wash-out curve. Absolute slope values of the wash-out curves after perfusion (Pwo) and ventilation (Vwo) were expressed as a percentage of the total for each lung. Correlation coefficients between V and Vwo, V and Pwo, P and Pwo were .695, .584 and .882 in normals and .610, .461 and .685 in patients, respectively. It is concluded that Pwo is influenced by both perfusion and ventilation; it may reflect the fractional contribution to the gas exchange and can be used in the prediction of residual lung function after lung resection.

Quantitative 99mTc-DTPA scintigraphy for determination of maxillary sinus drainage following Caldwell-Luc surgery.

Nine maxillary sinuses of 8 patients who had undergone Caldwell-Luc surgery (CWL) were injected with 100-125 microCi 99mTc-DTPA in 0.2 ml from the gingivo-buccal sulcus, passing through the canine fossa window. Sinus half-emptying times and percent contribution of the natural ostium (NO) and the naso-antral window (NA) to the clearance from the sinus were calculated, using time-activity curves as well as the activity of cotton wool plugs placed into the middle and lower conchae. Mean half-emptying times in patients in whom the mucosa had been removed were shorter than those in patients in whom it had been left in place. In the former group percent drainage through the NO was higher than that through the NA whereas in the latter group the opposite was the case. These findings are consistent with the thesis that if the mucosa is retained, the cilia continue their sweeping action towards the NO but if it is removed the NA gains importance in the drainage. This method is promising for the evaluation of maxillary sinus drainage following CWL.

Accumulation of 99mTc-glutathione in head and neck tumors.

Glutathione labelled with 99mTc was used to study blood clearance and normal distribution in 3 healthy volunteers and in 10 patients with biopsy-proven tumors in the head and neck region. Static scintigrams were obtained at 1, 3, 6, and 24 h. ROIs over tumors and normal soft tissues were compared to obtain T/N ratios. In normal subjects blood clearance reached a plateau at 6 h; no radio-activity accumulation in the head and neck region was observed. Only the cardiac blood pool, the liver, the kidneys and the urinary bladder were evident. Excretion was via the kidneys. Malignant tumors and metastases were well visualized in 7 patients (true-positive), starting at 1 h. The mean T/N ratio was 2.69 +/- 0.77. The best images were obtained at 3-6 h. 1 false-positive (granulamatous reaction), 1 false-negative (malignant epithelial tumor in the radix of tongue) and 1 true-negative (angiofibroma) results were obtained. 99mTc-GSH is a potential radiopharmaceutical for the scintigraphic visualization of head and neck tumors. Further clinical studies are warranted to show its sensitivity and accuracy.

Internal mammarial lymphoscintigraphy with SPECT after ultrasound-guided injection of 99mTc-dextran.

Twenty-two women with stage II or III breast cancer were evaluated by SPECT to determine the number, size, three-dimensional localization and depth from skin surface of the internal mammary lymph nodes for accurate radiotherapy portal planning. The results were also compared with those of planar imaging (PI). Two-step injections of 99mTc-dextran were made under ultrasound guidance into the anterior sheath of the M. rectus abdominis first at the ablation side. 1.5 h thereafter an anterior planar view was obtained to evaluate cross drainage (13.6% was observed). Then, the second injection was done at the opposite side in the same manner. Planar and tomographic images were obtained 1.5 h after the second injection. Similar values were obtained for the depth from skin surface, distance from the midline and diameter of the lymph nodes with both PI and SPECT. The total number of nodes in 22 patients detected by SPECT was higher (138) than that from PI (129), the difference being statistically significant (0.005 greater than p greater than 0.0005).

Left ventricular dysfunction and blood glycohemoglobin levels in young diabetics.

Left ventricular function including regional wall motion (RWM) was evaluated by 99mTc first-pass and equilibrium gated blood pool ventriculography and glycohemoglobin (HbA1c) blood levels determined by a quantitative column technique in 25 young patients with insulin-dependent diabetes mellitus without clinical evidence of heart disease, and in healthy controls matched for age and sex. Phase analysis revealed abnormal RWM in 19 of 21 diabetic patients. The mean left ventricular global ejection fraction, the mean regional ejection fraction and the mean 1/3 filling fraction were lower and the time to peak ejection, the time to peak filling and the time to peak ejection/cardiac cycle were longer in diabetics than in controls. We found high HbA1c levels in all diabetics. There was no significant difference between patients with and without retinopathy and with and without peripheral neuropathy in terms of left ventricular function and HbA1c levels.

Visualization of bone pathologies and lung cancer with 99mTc-glucose phosphate: a comparative study.

Glucose phosphate (GP) labelled with 99mTc was used to obtain scintigraphic images of bone lesions in one group of patients (n = 28) and of lung tumors in another (n = 35). All bone lesions detected by 99mTc-MDP were also demonstrated by 99mTc-GP; all lung tumors except 4 were detected by 99mTc-GP, the failure rate being about the same as that for 67Ga. The use of 99mTc-GP is preferable to that of 99mTc-MDP because the former does not accumulate in normal bone; the advantage of 99mTc-GP over 67Ga lies in its better physical characteristics and in the fact that the result of the study is available within a few hours rather than three days.

Scintigraphic visualization of acute pancreatitis in cats with 99Tcm-citrate.

The accumulation of 99Tcm-citrate in abscesses and arthritic joints has previously been demonstrated. In the present study its usefulness was evaluated in 10 mongrel cats with acute pancreatitis induced by metronidazole infusion. Five cats, used as normal controls, were given physiological saline. All 15 cats were injected intravenously with 185 MBq 99Tcm-citrate. Scintigrams were obtained at 30 min intervals up to 2 h after injection by a gamma camera. The cats were then sacrificed. Tissue samples were obtained, weighed and counted against a 1/1000 dilution of the injected dose. In normal cats the kidneys and the urinary bladder were the only organs that could be visualized. In acute pancreatitis the pancreas and its exudate in the abdomen were also evident on the images. The pancreas to other neighbouring organ ratios increased 2.3-9.7 fold in acute pancreatitis compared to normal controls. Gross autoradiograms showed localization of radioactivity in the lobules of pancreas. Histologic examination of sections of pancreas demonstrated oedema, haemorrhage and some fat necrosis in pancreatic parenchyma, confirming acute pancreatitis. In conclusion, it has been demonstrated that acute pancreatitis in cats can be visualized scintigraphically with 99Tcm-citrate.

Functional assessment of human gastrointestinal tract using 99Tcm-latex particles.

99Tcm-latex particles (LP) is a newly developed radiopharmaceutical for the evaluation of the gastrointestinal (GI) tract. Following oral ingestion, it passes through the entire GI tract undissolved. The purpose of the present investigation was to introduce the clinical application of 99Tcm-LP. A group of 11 healthy volunteers was studied. Following a 12 h fast, the subjects were given 150 ml of water containing 37 MBq of 99Tcm-LP orally. Dynamic images up to 2 h were recorded to document temporal progression of radioactivity. Static images of the abdomen and whole body were taken at intervals. In normal subjects the tracer arrival times at the caecum and sigmoid colon were 3.2 +/- 0.9 and 11.2 +/- 3.2 h, respectively. The average t1/2 value for gastric emptying, 50% colonic filling and small bowel transit time were found to be 21.6 +/- 5.6, 233 +/- 72 and 211 +/- 66.4 min, respectively. In conclusion, 99Tcm-LP has the potential of providing functional information of the GI tract.

Clinical evaluation of metastases of malignant melanoma imaging with 99Tcm-glutathione and 99Tcm-anti-melanoma antibody: a comparative study.

The aim of this investigation was to test for the scintigraphic detection of metastases of malignant melanoma with a new radiopharmaceutical, 99Tcm-glutathione (99Tcm-GSH), in comparison with 99Tcm-anti-melanoma antibody (99Tcm-AMAb). Glutathione was labelled with 99Tcm by a Sn2+ reduction method with an efficiency of > 99% as determined by instant thin layer chromatography (ITLC). Anti-melanoma antibody was obtained as a kit from SORIN (Italy) and labelled with 99TcmO-4. Forty-three patients with a total of 55 biopsy-proven metastatic melanoma foci, 1 ocular melanoma and 20 benign pathologic foci, also confirmed by ultrasound, computed tomography and magnetic resonance imaging, were included in the study after giving their informed consent. Following the intravenous (i.v.) injection of 500 MBq 99Tcm-AMAb, scintigraphic images of the involved areas were obtained 6 h post-injection. Three days later, the same patients were given 500 MBq 99Tcm-GSH i.v. and images were obtained 6 and 24 h post-injection. The images were classified as positive (focal abnormal accumulation) or negative. Quantitative evaluation was also applied. Regions of interest were drawn over the involved areas and nearby soft tissues and the target-to-nontarget (T/NT) ratios obtained with 99Tcm-AMAb (T/NT: 1.92 +/- 0.2) and 99Tcm-GSH (T/NT: 1.84 +/- 0.2) were compared (0.1 < P < or = 0.3). The sensitivity (and specificity) of 99Tcm-AMAb and 99Tcm-GSH in the detection of malignant melanoma metastases were 91% (95%) and 84% (90%), respectively. Compared with 99Tcm-AMAb, the advantages of 99Tcm-GSH are lower levels of blood radioactivity, lower costs and easy in-house preparation. In conclusion, our results show that 99Tcm-GSH is a potentially useful radiopharmaceutical for the detection of metastases of malignant melanoma.

Double-phase Tc-99m-SestaMIBI SPECT imaging in a case of glomus jugulare tumor.

We performed a double-phase Tc-99m-SestaMIBI SPECT study on a patient who presented with a mass located at the skull base. The results were compared with double-phase T1-201 SPECT study. Early phase (30 min) SPECT images of both radiopharmaceuticals demonstrated increased radiotracer uptake in the region of the tumor. However, late images (180 min) revealed rapid wash-out of Tc-99m-SestaMIBI from the tumor, suggestive of a benign vascular tumor, while T1-201 images showed slower wash-out. Tc-99m-SestaMIBI SPECT findings were also confirmed by carotid angiography and biopsy, while a contemporaneous MRI scan was inconclusive in differentiating benign from malignant tumor. Initial and one-year follow-up whole body CT scans were negative for any metastatic sites, supporting the diagnosis of benign glomus jugulare tumor.

Can bone scintigraphy detect additional metastatic sites unrevealed by CT in patients with recurrent ovarian carcinoma?

A patient who presented with recurrent ovarian carcinoma with elevated levels of CA 125 was evaluated for skeletal metastases by routine whole body bone scintigraphy. Although no bone metastasis was visualized, there was intense accumulation of tracer in the soft tissues corresponding to the liver, pelvis, and intestinal/peritoneal surface, suggestive of metastatic disease. Although liver and pelvic soft tissue metastases were confirmed by CT and USG, intestinal/peritoneal metastases could not be disclosed by either modality.

Influence of immediate post-therapy bone scintigraphy in the assessment of response to therapy in a case of nasopharyngeal carcinoma.

A patient with undifferentiated stage IV (T3N3M0) nasopharyngeal carcinoma (WHO type III) underwent pre- and one-month post-therapy bone scintigraphy as part of an ongoing trial combining scintigraphic and radiographic modalities. The patient had advanced disease in the nasopharynx and bulky cervical lymph nodes at presentation. Initial bone scintigraphy performed 10 days prior to therapy was negative for bone metastases. Immediately after concomitant chemoradiotherapy, bone scintigraphy revealed distant metastases, whereas clinical assessment of disease disclosed complete response to therapy in the nasopharynx and cervical lymph nodes. The scintigraphic findings were also confirmed by a subsequent MRI scan of the corresponding regions.

Tl-201 uptake in brown tumors of hyperparathyroidism.

Tl-201 chloride bone scans were performed on nine patients with primary hyperparathyroidism just after Tl-201 and Tc-99m parathyroid subtraction scintigraphy. Bone lesions accumulate Tl-201, especially in sites of brown tumor formation. This was proven by the histopathologic examination of two patients. Eight patients had bone scans with Tc-99m MDP. The lesion-to-background ratio was quantified in seven patients for Tl-201 and in four patients for Tc-99m MDP. Tl-201 uptake of the lesions were quantified in two patients. The lesion-to-background ratio was 1.63 +/- 0.21 and 2.51 +/- 0.88 for Tl-201 and Tc-99m MDP, respectively. A Ga-67 citrate scan was performed on one patient, and the lesion-to-background ratio was 1.49 +/- 0.06. The accumulation of Tl-201 in brown tumors of bone might be due to increased blood flow and local metabolic activity. Tl-201 chloride was inferior to Tc-99m MDP in lesion detection. It is concluded that bone imaging with Tl-201 can easily be performed following parathyroid subtraction scintigraphy to delineate the sites of brown tumor formation.

The value of Tc-99m citrate scintigraphy in chronic osteomyelitis. An indicator of the involved bone.

The authors present a prospective analysis of Tc-99m MDP and Tc-99m citrate scintigraphy in 29 patients who were clinically suspected of having chronic osteomyelitis. All of the patients showed increased Tc-99m MDP uptake on bone scintigraphy involving the area of concern. However, Tc-99m citrate scintigraphy clearly identified the patients with osteomyelitis (N = 18) confirmed either by biopsy or clinical follow-up. Eleven patients who were free of osteomyelitis showed only minimal radiotracer uptake on Tc-99m citrate scintigraphy. These patients had other benign musculoskeletal diseases that were diagnosed by other imaging modalities. In addition to visually interpreting the scintigraphic images, a semi-quantitative analysis was performed by drawing regions of interest over the areas involved and the normal contralateral side, and patients with osteomyelitis were found to have lesion to nonlesion ratios of greater than 1.70. Because Tc-99m MDP is a nonspecific radiopharmaceutical for the evaluation of bone infection, other imaging agents have been investigated. Tc-99m citrate is a small molecule that makes it suitable to penetrate injured capillaries to the edema fluid known to be present in areas of infection. The authors conclude that Tc-99m citrate is a promising agent for localizing and showing the extent of bone infection that will help the surgeon to determine areas of debridement before surgery.

The visualization of pulmonary tuberculosis with Tc-99m (V) DMSA and Tc-99m citrate in comparison to Ga-67 citrate.

Two patients with active tuberculosis confirmed by chest radiography and positive sputum smears were included in this study to determine whether a Tc-99m labeled agent, such as DMSA or citrate could localize such lesions in comparison to Ga-67 citrate. Both patients had Tc-99m (V) DMSA, Tc-99m citrate, and Ga-67 citrate scanning at 1-day to 5-day intervals. Both patients had positive scan findings with all three radiopharmaceuticals. However, the quality of Tc-99m (V) DMSA scans was superior to Tc-99m citrate, which showed faint uptake. Tc-99m (V) DMSA may be a better alternative to Ga-67 citrate in the assessment of the activity and extent of tuberculosis.