Faculty Bibliography

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/CONCLUSIONS: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.

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/CONCLUSIONS:MIBI SPECT could be used as a screening test in predicting response to therapy in patients with NPC.

The intention of this prospective study was to compare the diagnostic potential of technetium-99m sestamibi (MIBI) and a novel radiotracer, 99mTc-Tetrofosmin (Tetro), for the assessment of primary nasopharyngeal carcinoma (NPC) and the differentiation of residual disease from post-therapy changes. A total of 38 patients underwent MIBI and Tetro single-photon emission tomography (SPET) imaging at initial presentation (n=22) or following therapy (n=16). The findings were correlated with computed tomography or magnetic resonance imaging (MRI) on a site-by-site basis. Tumour/background (Tm/Bkg) ratios were obtained on coronal sections. Biopsy (nine patients) and/or 12- to 24-month clinical follow-up data were available in the post-therapy group. All primary disease sites were accurately detected by both imaging studies. Although there was no statistical difference between the two imaging techniques in the detection of primary disease, MIBI was superior to Tetro in the detection of regional lymph node metastases (sensitivity: 95% vs 79%). Tetro and MIBI SPET were true-positive in all patients (n=7) with proven residual/recurrent disease. In nine patients who had no evidence of residual/recurrent tumour, MRI was false-positive in five while Tetro and MIBI SPET were false-positive in two and three patients, respectively. Tm/Bkg ratios were </=1.7 in all false-positive cases except one. Tetro, MIBI and MRI had specificities of 78%, 67% and 44%, and accuracies of 87.5%, 81% and 69%, respectively. The results of Tetro and of MIBI SPET were not statistically different from one another with regard to the prediction of residual/recurrent or metastatic NPC.

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.

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/CONCLUSIONS: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.

UNLABELLED:This study describes the physiological uptake of 18F-fluoro-2-deoxyglucose (FDG) by the laryngeal muscles secondary to activation of the patient's vocal folds and related laryngeal muscles during speech. METHODS:Twenty-four patients undergoing routine PET scans were randomized into two groups to ascertain the relationship between FDG uptake in the laryngeal region and speech. One group was assigned to talk and the other group remained silent during the injection and uptake period of FDG. RESULTS:FDG uptake in the laryngeal muscles in the scans was correlated with speech. Patients who spoke continually during the uptake period had high-grade FDG uptake, those who spoke intermittently had low-grade uptake and those who remained silent had no detectable increase in FDG uptake in the region of the larynx. CONCLUSION/CONCLUSIONS:The relationship between the degree of laryngeal muscle uptake and speech provides useful information to allow differentiation of physiological from pathological uptake in the neck.

RATIONALE AND OBJECTIVES/OBJECTIVE:The authors present preliminary findings on the diagnosis of renovascular hypertension with technetium-99m-ethylenedicysteine (99mTc-EC). METHODS:Thirty-nine patients referred to the nuclear medicine department with clinical evidence of renovascular hypertension were included in the study. Baseline and captopril scintigraphies were done on separate days after the injection of 185 MBq of 99mTc-EC. All patients had angiographic correlation and 9 patients were shown to have renal artery stenosis. RESULTS:Quantitative analysis of the data showed no significant changes of perfusion index (PI), split renal function (SRF), and effective renal plasma flow (ERPF) values between pre- and postcaptopril studies in patients with significant renal artery stenosis (P > 0.05). Baseline and postcaptopril values for PI, SRF, and ERPF were measured as 128 +/- 21 and 116 +/- 12 mL/minute, 47 +/- 1 and 50 +/- 2 mL/minute, and 250 +/- 18 and 231 +/- 20 mL/minute, respectively. However, time to maximum activity (Tmax), time to half maximum activity (T 1/2), time to two thirds of maximum activity (T 2/3), and residual cortical activity (RCA) values showed marked changes with a rising renogram curve (P < 0.05). Baseline and postcaptopril values for Tmax, T 1/2, T 2/3, and RCA were measured as 3.1 +/- 0.1 and 20.2 +/- 1 minute, 5.4 +/- 0.4 and 45.4 +/- 3.1 minutes, 3.1 +/- 0.2 and 33.7 +/- 4.1 minutes, and 27 +/- 4 and 215 +/- 34 minutes, respectively. All scintigraphic studies showed good correlation with angiography and no false-positive or false-negative results were observed. CONCLUSIONS:This preliminary study demonstrates that 99mTc-EC has good potential for the diagnosis of renovascular hypertension and that a single diagnostic criteria, specifically a rising renogram curve, seems adequate. However, the authors' initial results should be confirmed in a broader patient population.

The present study evaluated the ability of the anti-GD2 ganglioside monoclonal antibody 3F8 to target tumor sites in patients with small-cell lung cancer (SCLC). Of 12 patients entered into the trial, ten received intravenous 3F8 labeled with 2 or 10 mCi iodine-131. The first five patients had recurrent or progressive disease after chemotherapy. Subsequent patients were studied before starting chemotherapy. Radionuclide scans were performed on days 1, 2, and 3 post-infusion and once between day 5 and day 7. Four patients underwent single-photon emission tomography (SPET) imaging. Radionuclide scans demonstrated localization to all known sites of disease, other than small brain metastases in one patient. SPET/CT scan fusion images confirmed precise localization. No significant toxicity was observed. Mean serum half-life was 64.2 h. Analysis of specimens from one patient who died of unrelated causes 6 days post-infusion confirmed the scan results. The present study demonstrates that 3F8 targets SCLC sites in patients. Further studies of anti-GD2 antibodies with higher doses of antibody and radionuclide are warranted to evaluate their role in SCLC.

To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibody-radioisotope combinations should be used to deliver the highest tumor and the lowest normal tissue doses. In a mouse model, tumor and critical organ-absorbed doses delivered by different radioimmunoconjugates were calculated and compared. We used a Medical Internal Radiation Dosimetry (MIRD)-style mouse dosimetry model that incorporates cross-organ beta doses to make refined estimates of the radiation absorbed dose to tissues. Biodistribution data from neuroblastoma xenografted nude mice were used to estimate tumor, organ and bone marrow absorbed dose values for 90Y-3F8, 131I-3F8 and 131I-F(ab')2 fragments. Immunoreactive fractions of the radiolabeled antibodies were comparable. Although tumor uptake of the radioiodinated and radiometal labeled 3F8 was much higher than that of the radioiodinated F(ab')2 fragments (maximum percent injected dose per gram values were 39.4, 33.2 and 20.1 for 131I-3F8, 90Y-3F8 and 131I-F(ab')2, respectively), tumor to nontumor ratios were higher for radioiodinated fragments (with the exception of tumor to kidney ratio). For the minimum tumor dose necessary for complete ablation, the bone marrow received 195, 278 and 401 cGy for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor doses were 50.1, 232 and 992 cGy/MBq for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor to bone marrow dose, which is defined as the therapeutic index, was 21.5, 14.7 and 10.4 for 131I-F(ab')2, 131I-3F8 and 90Y-3F8. 131I-F(ab')2 fragments produced the highest therapeutic index but also the lowest tumor dose for radioimmunotherapy. Radiometal conjugated IgG produced the highest tumor dose but also the lowest therapeutic index.