Accuracy of FDG-PET/CT and paraneoplastic antibodies in diagnosing cancer in paraneoplastic neurological syndromes.

OBJECTIVE: There is still no consensus about whether to perform PET/CT to detect carcinoma in paraneoplastic neurological syndromes (PNS) in patients with or without antibodies. The aim of this study is to determine the diagnostic accuracy of PET/CT and antibodies in patients with PNS. MATERIAL AND METHODS: A retrospective study was conducted on patients with clinically suspected PNS between 2008 and 2013. The association between histopathological findings, paraneoplastic antibodies, and PET/CT findings were evaluated. Sensitivity and specificity for the detection of underlying malignancy were calculated for PET/CT and paraneoplastic antibodies. RESULTS: A total of 42 patients were analyzed. Of these 42 patients, 32 (75%) had a classical PNS, 6 (14%) had positive PET/CT findings, and 34 were tested for the presence of antibodies (anti-Hu Ab, anti-Yo Ab, and anti-Ri Ab). Twenty one of 34 patients had positive antibodies. Of the 6 patients with positive PET/CT findings, 6 had positive histopathological results. Among 21 patients with positive biomarkers, carcinoma was confirmed only in 5 patients. One patient with negative antibodies, but positive PET/CT findings, was diagnosed with a tumor. Gastric carcinoma was detected in 1 patient with negative PET/CT findings and antibodies during follow-up. Based on the results, PET/CT was found to have 85.71% sensitivity, 100% specificity, 100% positive and 97.22% negative predictive values in the detection of tumors. CONCLUSION: PET/CT has a certain diagnostic accuracy for detecting underlying malignancy in patients with PNS, regardless of the presence of paraneoplastic antibodies.

Decreased preoperative serum fibulin-3 levels in colon cancer patients.

OBJECTIVE: Fibulin-3 is known to play a role in tumor cell malignancy, invasion and metastasis, as well as in the clinical progression of tumors. This study aimed to assess serum fibulin-3 levels in patients with colon cancer compared with healthy controls and its relationship to demographics and tumor pathology. PATIENTS AND METHODS: A total of 80 patients (mean age, 58.99 years; 42% males) with colon cancer and 50 controls (mean age, 57.75; 55% males) were included. Serum levels of fibulin-3 were determined using a commercially available sandwich ELISA (Enzyme-Linked ImmunoSorbent Assay). RESULTS: Preoperative serum fibulin-3 levels were significantly lower in the group of patients with colon cancer (mean, 35.91 ng/mL; range, 10-73 ng/mL) compared with the control group (mean, 96.68 ng/mL; range, 57-168 ng/mL). CONCLUSIONS: It was concluded that fibulin-3 is expressed at a lower level in colon cancer, and it can serve as a marker for advanced colon cancer.

Comparison of FDG and FDG-labeled leukocytes PET/CT in diagnosis of infection.

UNLABELLED: The aim of this study is to compare FDG and FDG-labeled leukocyte (WBC) PET/CT in the diagnosis of infection using different SUV and visual thresholds for interpretation. Patients, material, method: 49 consecutive patients (27 men, 22 women, mean age: 55.7 years, range: 16-89 years) with suspected musculoskeletal infection (n = 34), vascular graft infection (n = 5), aortitis (n =1 ), endocarditis (n = 1), mass lesion which is suspicious for infection or malignity (n = 6), and fever of unknown origin (n = 2) underwent both FDG and WBC-PET/CT. Images were evaluated by both visual analysis (grade 1-3) according to uptake intensity and quantitative grading (grade 1-3) based on lesion to background SUVmax values. Final diagnosis was made by histopathological, microbiological analysis or clinical-radiological work-up. RESULTS: The diagnosis of infection was made in total 24 patients, of whom 14 were diagnosed by histopathological and the rest by clinical-radiological work-up. WBC-PET/CT imaging with the visual threshold of 1b as infection positivity (for truncal lesions uptake equivalent to liver or lumbar vertebrae uptake; for extremity lesions uptake significantly higher than neighbouring soft tissue uptake or higher than neighbouring bone marrow uptake) was found to have the highest diagnostic accuracy (AUC: 0.874, CI: 0.771-0.997, p < 0.001). The optimal SUV threshold was found to be 8.8 (p = 0.006; sensitivity: 72.7%, specificity: 82.8) and 5.3 (p < 0.001; sensitivity: 81.8%, specificity: 79.3%) for FDG and WBC-PET/CT, respectively by ROC curve analysis. CONCLUSION: WBC-PET/CT is more valuable than FDG PET/CT in the imaging of infection. Visual threshold of >1b seems to be more suitable for detection of infection.

Unexpected bone marrow uptake of thallium-201 in nonsecretory myeloma.

A 43-yr-old man was referred for any possible parathyroid abnormality that could explain his hypercalcemia and slightly increased parathormone levels. The thallium-technetium scan showed a diffuse abnormal thallium uptake incidentally in the bone marrow, otherwise parathyroid scan appearance was normal. He had an essentially normal bone scan, although subsequent nanocolloid scintigraphy demonstrated bone marrow expansion. Further investigations, including a bone marrow aspiration biopsy, confirmed the diagnosis of nonsecretory myeloma. This finding suggests that 201Tl imaging can be a useful tool to investigate those patients suffering from similar myeloid disorders causing bone marrow hyperplasia.

Validation of renal output efficiency as an objective quantitative parameter in the evaluation of upper urinary tract obstruction.

This is a preliminary study of the parameter, renal output efficiency (ROE), for the quantitation of furosemide (frusemide) response in diuresis renography. This is calculated by a technique independent of variations in uptake rate by the kidneys. Eleven healthy volunteers and 34 patients suspected of upper urinary obstruction were subjected to gamma camera studies using 99mTc-MAG3 and a standard protocol. Furosemide was given at 18 min after the study was started. The ROE was calculated in each kidney and the results were correlated with final diagnosis. The range of ROE in healthy individuals varied between 82% and 98% (mean = 91.6%); while obstructed kidneys showed significantly reduced values (p < 0.001) ranging between 30% and 76% (mean = 56%). In the diagnosis of urinary obstruction, the ROE has a sensitivity of 91%, specificity of 94% and accuracy of 94%. ROE complements conventional diuresis renography and provides better diagnostic yield in patients with impaired renal function.

Clinical comparison of technetium-99m-EC, technetium-99m-MAG3 and iodine-131-OIH in renal disorders.

UNLABELLED: Technetium-99m-ethylenedicysteine has recently been developed for renal function studies. The pharmacokinetics of 99mTc-EC were studied by constant infusion technique and compared with 99mTc-MAG3 and 131I-OIH in 11 patients with various renal disorders. METHODS: After giving a 7.4 MBq 131I-OIH and 90-110 MBq 99mTc-EC or 99mTc-MAG3 bolus, a constant infusion (1MBq/ml 99mTc-agent and 0.07 MBq/m 131I-OIH was started. Sixteen blood and five urine samples were obtained over three hr. RESULTS: The renal clearance of 99mTc-EC was higher than that of 99mTc-MAG3. The 99mTc-EC/OIH and 99mTc-MAG3/OIH ratios were 0.75 +/- 0.05 and 0.55 +/- 0.10 (p = 0.00087), respectively. The distribution volume of 99mTc-EC was also higher than that of 99mTc-MAG3 (15722 +/- 4644 and 9509 +/- 2788 ml/1.73m2, respectively; p = 0.072). The 99mTc-EC/OIH and 99mTc-MAG3/OIH distribution volume ratios were 1.03 +/- 0.14 and 0.55 +/- 0.10, respectively (p = 0.0003). The 60-min excretion values of 99mTc-EC and 99mTc-MAG3 were compared to that of OIH. The 99mTc-EC/OIH and 99mTc-MAG3/OIH excretion ratios were 0.96 +/- 0.06 and 1.07 +/- 0.10, respectively (p = 0.162). The protein binding of 99mTc-EC and OIH were found to be 34% +/- 4 and 66% +/- 5, respectively (p < 0.0001). The red cell binding of 99mTc-EC was negligible (3% +/- 1.2) in comparison to OIH (27% +/- 3; p < 0.0001). CONCLUSION: This limited study demonstrates the pharmacokinetic and renal clearance properties of 99mTc-EC. This agent has good potential for renal function evaluation.

Brain SPECT evaluation of the visual cortex in amblyopia.

UNLABELLED: In amblyopia, the number of visual cortical neurons are reduced and abnormal or absent sensitivity to retinal light stimulation of the amblyopic eye is demonstrated. Ten amblyopic patients were studied to evaluate the response of the visual cortex to visual stimulation. METHODS: All patients with unilateral amblyopia received 500-550 MBq 99mTc-HMPAO during visual stimulation. Strobe light flashing was used as the stimulus for five patients and a checkerboard pattern reversal was used in the other five patients, closing one eye. For both groups a 2-Hz frequency was used. One week later, the same procedure was repeated with the opposite eye closed. SPECT images were reconstructed with prefiltering techniques and sliced along the orbitomeatal line. RESULTS: For all patients, the amblyopic eye demonstrated less radioactivity in the visual cortex than in the normal eye. The mean cerebral-to-cerebellar ratios were 0.95 +/- 0.05 and 1.09 +/- 0.07 for amblyopic and normal eyes, respectively (p < 0.0001). CONCLUSION: Visual cortex response of the amblyopic eye to light stimulation was severely reduced when compared to the normal eye.

Evaluation of technetium-99m-ethylenedicysteine in renal disorders and determination of extraction ratio.

UNLABELLED: This article evaluates the clinical usefulness of 99mTc-ethylenedicysteine (EC) in patients with various renal disorders. In addition, extraction ratios of 99mTc-EC in five volunteers were also determined. METHODS: Twenty patients were intravenously injected with 200 MBq 99mTc-EC and 2.5 MBq [131I]orthoiodohippurate (OIH) simultaneously and 11 blood samples were withdrawn within 60 min. Plasma clearance was determined on the basis of a two-compartment model. Imaging was performed in the posterior projection by acquiring three sets of images. Extraction ratios were determined from the blood samples obtained from the renal vein and abdominal aorta. RESULTS: Renal clearance of 99mTc-EC was significantly lower than that of OIH (p = 0.0003) with good correlation (r = 0.93). Volume distributions of 99mTc-EC and OIH were 26584 +/- 10807 ml/1.73 m2 and 23148 +/- 7602 ml/1.73 m2, respectively (p = 0.047). The clearance half-lives of 99mTc-EC and OIH were 98 +/- 54 min and 74 +/- 54 min, respectively (p = 0.049). Protein binding of 99mTc-EC (33 +/- 3.2%) was significantly less than that of OIH (62 +/- 2.8%) (p < 0.0001). Red blood cell binding of 99mTc-EC was almost negligible (5.7 +/- 4.3%). Similar extraction ratios were obtained from blood (0.68 +/- 0.08) and plasma (0.70 +/- 0.07) (p = 0.062). The 60-min excretion fractions were similar for 99mTc-EC and OIH, with values of 50% +/- 20% and 51% +/- 19%, respectively (p = 0.9). CONCLUSION: Technetium-99m-EC is a suitable radiopharmaceutical for routine renal dynamic studies. Although the biological behavior of 99mTc-EC seems to be different from that of OIH, their clearances demonstrate high correlation. Technetium-99m-EC provides excellent quality images and has high potential in the evaluation of quantitative renal functions.

Technetium-99m-MIBI scintigraphy in pulmonary tuberculosis.

UNLABELLED: We investigated the usefulness of 99mTc-methoxyisobutylisonitrile scintigraphy in patients with known or suspected pulmonary tuberculosis (PTB) in comparison with radiological and bacteriological findings. METHODS: Thirty-six patients aged 13-59 yr were scanned 15 and 60 min after intravenous injection of 370 MBq (10 mCi) 99mTc-methoxyisobutylisonitrile. Twenty-four patients had active PTB proven by chest radiograph and sputum examinations, two had miliary tuberculosis and ten were suspected of having relapsed PTB with negative sputum examinations and indeterminate chest radiographs. In 12 patients 99mTc-MIBI imaging was repeated 1-3 mo after chemotherapy. RESULTS: Of 24 patients with active localized PTB, 22 (92%) showed increased focal uptake of 99mTc-MIBI, but two patients with minimal infiltration on chest radiographs had no accumulation of 99mTc-MIBI. Both patients with miliary PTB showed diffuse 99mTc-MIBI uptake in the lungs. Among 10 patients with suspicion of relapse, 99mTc-MIBI scans were true-positive in 4 of 5 patients (80%) with culture-proven tuberculosis and false-positive in 2 of 5 (40%) patients with negative sputum cultures. For repeat imaging, 6 of 10 patients with active localized PTB showed reduced MIBI uptake, which correlated with chest radiograph findings, and one patient had increased MIBI uptake again concordant with clinical and radiological findings which were suggestive of resistance to first line chemotherapy of tuberculosis. The other three patients showed no significant scintigraphic changes despite clinical and partial radiological regression. CONCLUSION: Active PTB granulomas generally present considerable 99mTc-MIBI uptake that is most probably related to disease activity. Therefore, 99mTc-MIBI scanning could be used in the detection and follow-up of active PTB as a complement to routine techniques.

Comparison of 99mTc-methoxyisobutyl isonitrile and 201T1 scintigraphy in visualization of suppressed thyroid tissue.

UNLABELLED: Both (201)TI and (99m)Tc-methoxyisobutyl isonitrile (MIBI) have been used in the visualization of suppressed thyroid tissue in patients with autonomously functioning thyroid nodules (AFTNs). It has been suggested that thyroid-stimulating hormone (TSH) control is not a major determinant of both tracers. However, the mechanism of thyroid uptake of these agents is controversial. In this study, we compared (201)TI and MIBI in the visualization of suppressed thyroid tissue in patients with a solitary toxic AFTN. METHODS: Thirty-two patients (13 triiodothyronine [T3] and 19 T3 + levorotatory thyroxine [T4] hyperthyroid patients) with toxic AFTNs visualized on (99m)Tc-pertechnetate scanning were included in the study. All patients underwent MIBI and (201)TI thyroid scintigraphy within a 3-d interval. The scintigrams were analyzed both visually and semiquantitatively. For the semiquantitative analysis, regions of interest (ROIs) were generated over the nodule (N) and contralateral normal lobe (E), and the mean counts in each ROI were calculated. RESULTS: The N/E uptakes (mean +/- SD) for pertechnetate, MIBI, and (201)TI were 11.37 +/- 4.53, 4.76 +/- 1.38, and 1.63 +/- 0.15, respectively, in T3 + T4 hyperthyroid patients and 9.46 +/- 3.64, 2.73 +/- 0.63, and 1.57 +/- 0.23, respectively, in T3 hyperthyroid patients. Our results showed that (201)TI uptake of suppressed thyroid tissue compared with AFTN was more prominent and significantly higher than that of MIBI for both groups of patients (P = 1.08E-05 for T3 and 6.15E-09 for T3 + T4 hyperthyroidism). There was no significant difference for either pertechnetate or (201)TI (P > 0.05) when the N/E uptakes of both groups of patients were compared. However, the N/E uptake of MIBI in T3 + T4 hyperthyroid patients was significantly higher than that in T3 hyperthyroid patients (P = 6.69E-06). CONCLUSION: Clear visualization of suppressed thyroid tissue with both (201)TI and MIBI in patients with low serum concentrations of TSH suggests that TSH is not a major factor in the thyroid uptake of either agent. (201)TI is superior to MIBI in the visualization of suppressed thyroid tissue in patients with a toxic thyroid nodule. An increased rate of metabolism in the follicular cells of AFTNs in T3 + T4 hyperthyroid patients compared with that in T3 hyperthyroid patients might be responsible for the higher N/E for MIBI compared with that for (201)TI.

Usefulness of 99mTc-ciprofloxacin (infecton) scan in diagnosis of chronic orthopedic infections: comparative study with 99mTc-HMPAO leukocyte scintigraphy.

UNLABELLED: 99mTc-labeled ciprofloxacin (infecton) has been developed for detecting infectious foci, which localize in high concentrations in living bacteria. Other studies performed with various infections in animals and humans have found that infecton is a promising agent with better specificity for bacterial infections than white blood cell (WBC) scans. In this study, we evaluated the efficacy of infecton scintigraphy for detecting chronic bone and joint infections. METHODS: Fifty-six sites with suspected bone or joint infection were examined with 99mTc-WBC and infecton scans in 51 patients. Of these patients, 21 had prosthetic implant materials. Biochemical, radiologic, and microbiologic data and clinical outcomes also contributed, along with the results from scintigraphic techniques, in determining the presence or absence of infection. Scintigraphic images were produced at 1 and 4 h after injection of 370-400 MBq infecton or 185-200 MBq 99mTc-hexamethylpropyleneamine oxime (HMPAO)-WBCs. For each patient, there were at least 2 d and at most 7 d between scintigraphic studies. RESULTS: There were 30 true-positive, 4 false-positive, 20 true-negative, and 2 false-negative results with infecton. With 99mTc-HMPAO-WBCs, the results were 20, 1, 23, and 12, respectively. Values for sensitivity, specificity, and accuracy were 94%, 83%, and 89%, respectively, with the infecton scan and 63%, 96%, and 77%, respectively, with WBC scanning. Differences between the two agents were statistically significant (P < 0.001). Infecton and WBC scan results were in general concordance for 43 of 56 sites (77%). Infecton results for vertebral infections were the most notable findings in this study, despite the limited number of patients with this condition. Infecton scans were positive for hot spots in five of six patients with vertebral osteomyelitis. WBC scans showed photon-deficient areas in four of these same patients and normal distribution in the remaining two patients. CONCLUSION: Infecton is a useful agent for detecting infectious foci in bones and joints. Moreover, the infecton scan seems to be a more powerful tool in diagnosing vertebral infections than WBC scintigraphy.

Prospective validation of single plasma sample 99mTc-ethylenedicysteine clearance in adults.

UNLABELLED: 99mTc-L,L-ethylene, L, dicysteine (EC) clearance shows strong correlation with orthoiodohippurate clearance, and it is possible to estimate effective renal plasma flow from 99mTc-EC clearance. In routine clinical studies, it is practical to use the one or two plasma sample method instead of multiple plasma samples for clearance determination. A single-sample technique was developed for 99mTc-EC, and a regression formula was generated. A prospective study tested the validity of this regression formula. METHODS: The study population was composed of 26 patients with a wide range of renal function. Multiple plasma sample 99mTc-EC clearances were calculated from all patients using the open two-compartment model. Single plasma sample clearances were also determined from the 54-min plasma sample using the regression formula published previously. RESULTS: The multiple-sample plasma clearance of 99mTc-EC ranged from 46 to 668 mL/min with a mean of 300.76 +/- 150.73 mL/min. The clearances obtained from the 54-min plasma sample ranged from 49 to 699 mL/min, with a mean of 297.39 +/- 152.23 mL/min. There was an excellent correlation between the clearances obtained by the two techniques (r = 0.99, slope = 0.9911). The standard error of estimation was found to be 25.9 mL/min. CONCLUSION: This study suggests that 99mTc-EC clearance can be estimated from 54-min plasma samples with an acceptable error of estimation for most routine clinical studies.

Predictive value of captopril transit renography in essential hypertension and diabetic nephropathy.

Captopril renography was utilized to assess the presence of angiotensin II dependent renovascular dysfunction in (1) 28 patients with mild to moderate essential hypertension (EH) with unimpaired renal function, and (2) 25 hypertensive patients with diabetic nephropathy (HDN). These studies were classified according to the diagnostic criteria outlined by the Working Party on Diagnostic Criteria of Renovascular Hypertension with Captopril Renography and the mean parenchymal transit time (MPTT) was used as an index for detecting the presence of angiotensin II dependent renal haemodynamic change. Patients with EH showed non-significant or non-specific alterations in the MPTT. Four patients in the HDN group showed a significant prolongation of MPTT in the presence of renin-angiotensin-aldosterone activation due to renal artery stenosis, and the other patients in this group showed a significant decrease in MPTT after captopril, consistent with increased blood flow and improved tubular transport function in the presence of microangiopathy only. We conclude that addition of MPTT to the standard diagnostic criteria of captopril renography may be helpful in predicting the beneficial or detrimental impact of angiotensin II inhibition treatment in HDN and in limiting the test protocol in EH to one post-captopril study.

The role of 99Tcm-tetrofosmin in the evaluation of thyroid nodules.

Various radionuclides, including 67Ga, 201Tl and 99Tcm-sestamibi, have been used to differentiate benign from malignant thyroid nodules. 99Tcm-tetrofosmin, a lipophilic cationic radiotracer, and 99Tcm-sestamibi have also been reported to accumulate in thyroid tumours. In this study, we evaluated the role of 99Tcm-tetrofosmin in the differentiation of malignant from benign thyroid nodules. Seventy-nine patients with solitary non-functioning thyroid nodules were included in the study. Fine-needle aspiration biopsy was performed in all patients. Sixty patients were subsequently operated on and 19 patients refused surgery. After the injection of 370 MBq 99Tcm-tetrofosmin, static images at 5, 30, 60, 120 and 180 min were acquired. Both visual and semi-quantitative analysis was performed. On visual interpretation, the nodules with late retention were classified as positive for malignancy and nodules without late retention were classified as negative for malignancy. In the semi-quantitative analysis, regions of interests were drawn over the nodule and contralateral normal thyroid tissue. The average number of counts was recorded and tumour-to-normal thyroid tissue ratios calculated. Post-operative histology revealed 19 malignant and 41 benign nodules. Of the benign nodules, adenomas behaved similarly to the malignant nodules with late retention of tracer, while adenomatous nodules revealed no late retention on delayed images and could be differentiated from malignant tumours. In the semi-quantitative analysis, there was a significant difference in tumour-to-normal tissue ratios for adenomatous nodules and malignant tumours as well as adenomas. We conclude that it is not possible to differentiate between malignant and benign thyroid nodules with 99Tcm-tetrofosmin. However, 99Tcm-tetrofosmin scintigraphy is helpful in selecting nodules that can be cured by surgical intervention.

The value of serum prostate specific antigen and other parameters in detecting bone metastases in prostate cancer.

The cut-off value of serum prostate-specific antigen (PSA) level in prediction of bone metastases and the correlation of serum PSA with the clinical stage, grade, score and the rate of bone metastases have been investigated in cases of prostate cancer (PCa). The study population consisted of 160 patients with histologically proven PCa between April, 1993 and August, 1996. The negative predictive value and the sensitivity were the highest (94%) in patients with a serum PSA value less than 10 ng/ml. We claim that in patients with PSA values less than 10 ng/ml whole body bone scan is not necessary.

FDG PET/CT in monitoring treatment of retroperitoneal fibrosis.

Retroperitoneal fibrosis is an uncommon disease characterized by inflammatory fibrosis typically surrounding abdominal aorta and iliac arteries. The glucose analogue F18-fluorodeoxyglucose can be used to image inflammatory cell activity non-invasively by PET. In this report we investigated the usefulness of the FDG PET/CT in the disease activity and therapy response evaluation of retroperitoneal fibrosis.