Modified PISAPED Criteria in Combination with Ventilation Scintigraphic Finding for Predicting Acute Pulmonary Embolism.

This prospective clinical study aimed at assessing three pulmonary scintigraphic algorithms to detect acute pulmonary embolism (PE): Lung ventilation/perfusion (V/Q) scintigraphy along with modified prospective investigation of pulmonary embolism diagnosis (PIOPED) criteria; lung perfusion scintigraphy along with prospective investigative study of acute pulmonary embolism diagnosis (PISAPED) criteria; and lung perfusion scan in combination with ventilation scan, along with modified PISAPED criteria, which were newly developed. Patients with suspicion of PE were eligible for this study if they had no abnormal chest x-ray. Their diagnostic workup included a clinical assessment, a pulmonary V/Q scintigraphy, and CT pulmonary angiography (CTPA), as well as a clinical outcome assessment over a period of 24 weeks. Referred to the final clinical diagnosis of patients, the sensitivity and specificity of each algorithm were evaluated. The diagnostic performance of each algorithm by the area under the maximum likelihood fitted receiver operating characteristic (ROC) curve was determined. With respect to the PISAPED criteria, the sensitivity was 60.8% and specificity was 87.3%. No patient was classified into nondiagnostic category. The PIOPED criteria showed that the sensitivity was 95.0% and specificity was 88.2%, while 57.4% of the patients were in nondiagnostic category. The areas under the ROC curve constructed from the PISAPED criteria results and the modified PIOPED criteria results were 0.734 and 0.859 (P < 0.01), respectively. The modified PISAPED criteria demonstrated that the sensitivity was 83.8% and specificity was 89.1%. No patient was classified into nondiagnostic category. The area under the ROC curve constructed from modified PISAPED criteria was 0.864 (P < 0.01). Perfusion scans used with ventilation scans and modified PISAPED criteria may increase the diagnostic accuracy of pulmonary scintigraphy for acute PE, compared with the two major algorithms.

The ability of 18F-choline PET/CT to identify local recurrence of prostate cancer.

PURPOSE: To determine when 18F-choline PET/CT can truly identify local recurrence of prostate cancer. METHODS: 1031 patients from 3 European centers underwent (18)F-choline PET/CT (FCH PET/CT) for recurrent disease; 131 subjects (12.7%) showed a positive FCH uptake in the prostatic gland or prostatic fossa. Median age was 72 years (range 48-87 years), and the median PSA level at the time of FCH PET/CT scan was 4.41 ng/mL (0.22-18.13 ng/mL). 45 patients (34.4%) had a Gleason score (GS) >7, and the residual subjects had a GS ≤ 7. The assessment of true or false-positive FCH PET/CT findings was made by magnetic resonance imaging (n = 34) and/or biopsy in 75/131 cases. A χ (2) test and a Z Kolmogorov-Smirnov test were used to assess the correlation between clinical variables (age, PSA, GS, type of therapy) and FCH PET/CT findings. RESULTS: FCH PET/CT resulted truly positive (TP) for recurrent disease in the prostatic gland/fossa in 59/75 patients (79%) and falsely positive (FP) in 16 subjects (21%). The median value of PSA at the time of FCH PET/CT scan was higher in TP as compared to FP, although not statistically significant (4.76 vs. 3.04 ng/mL p > 0.05). Similarly, median age, GS categories, and the type of therapy were similar between the two groups (p > 0.05). However, when matching GS categories and PSA values, we found that the number of patients with TP findings were higher in the case of a PSA > 2 ng/mL, independently from the GS (ranging between 74% and 92%). Conversely, FP rate ranged between 50% and 65% in patients with a PSA ≤ 2 ng/mL, especially in the case of GS ≤ 7, whereas FP was around 25% in those with a GS >7 and PSA > 2 ng/mL. CONCLUSIONS: FCH PET/CT has a limited role in evaluation of prostatic gland/fossa recurrence, due to the physiological biodistribution of the radiopharmaceutical agent. However, in 70-90% of patients with a PSA >2 ng/mL, independently from GS, a focal FCH uptake is compatible with a true local recurrence.

Hypoxia PET Tracers in EBRT Dose Planning in Head and Neck Cancer.

Over the years, external beam radiotherapy (EBRT) has been used in the treatment management of many malignancies, including head and neck squamous cell carcinomas (HNSCC). Hypoxia is a common feature in HNSCC. Hypoxic segments in HNSCC have proven to be more resistant to radiotherapy. The ability to identify hypoxia using SPECT and PET tracers has been investigated since the late 1970s. Nitroimidazole-based compounds labelled with positron emitters have been developed to more specifically image hypoxia. This article reviews the current data from research publications on(18)F-FMISO, (18)F-FAZA, (18)F-EF5 and (64)Cu-ATSM.

Gleason score at diagnosis predicts the rate of detection of 18F-choline PET/CT performed when biochemical evidence indicates recurrence of prostate cancer: experience with 1,000 patients.

UNLABELLED: The objective of this study was to explore the ability of the initial Gleason score (GS) to predict the rate of detection of recurrent prostate cancer (PCa) with (18)F-choline PET/CT in a large cohort of patients. METHODS: Data from 1,000 patients who had undergone (18)F-choline PET/CT because of biochemical evidence of relapse of PCa between 2004 and 2013 were retrieved from databases at 4 centers. Continuous data were compared by the Student t test or ANOVA, and categoric variables were compared by the χ(2) test. Univariable and multivariable analyses were performed by logistic regression. RESULTS: The GS at diagnosis was less than or equal to 6 in 257 patients, 7 in 347 patients, and greater than 7 in 396 patients. The results of 645 PET/CT scans were positive for PCa recurrence. Eighty-one percent of the positive PET/CT results were found in patients with a PSA level of greater than or equal to 2 ng/mL, 43% were found in patients with a PSA level of 1-2 ng/mL, and 31% were found in patients with a PSA level of less than or equal to 1 ng/mL; 78.8% of patients with positive PET/CT results had a GS of greater than 7. The results of (18)F-choline PET/CT scans were negative in 300 patients; 44% had a GS of less than or equal to 6, 35% had a GS of 7, and 17% had a GS of greater than 7. PET/CT results were rated as doubtful in only 5.5% of patients (median PSA, 1.8 ng/mL). When the GS was greater than 7, the rates of detection of (18)F-choline PET/CT were 51%, 65%, and 91% for a PSA level of less than 1 ng/mL, 1-2 ng/mL, and greater than 2 ng/mL, respectively. In univariable and multivariable analyses, both a GS of 7 and a GS of greater than 7 were independent predictors for positive (18)F-choline PET/CT results (odds ratios, 0.226 and 0.330, respectively; P values for both, <0.001). CONCLUSION: A high GS at diagnosis is a strong predictive factor for positive (18)F-choline PET/CT scan results for recurrent PCa, even when the PSA level is low (i.e., ≤1 ng/mL).

Incidental uptake of (18)F-fluorocholine (FCH) in the head or in the neck of patients with prostate cancer.

BACKGROUND: Positron emission tomography-computed tomography (PET/CT) with (18)F-fluorocholine (FCH) is routinely performed in patients with prostate cancer. In this clinical context, foci of FCH uptake in the head or in the neck were considered as incidentalomas, except for those suggestive of multiple bone metastases. RESULTS: In 8 patients the incidental focus corresponded to a benign tumour. The standard of truth was histology in two cases, correlative imaging with MRI in four cases, (99m)Tc-SestaMIBI scintigraphy, ultrasonography and biochemistry in one case and biochemistry including PTH assay in one case. The final diagnosis of benign tumours consisted in 3 pituitary adenomas, 2 meningiomas, 2 hyperfunctioning parathyroid glands and 1 thyroid adenoma. Malignancy was proven histologically in 2 other patients: 1 papillary carcinoma of the thyroid and 1 cerebellar metastasis. CONCLUSIONS: To the best of our knowledge, FCH uptake by pituitary adenomas or hyperfunctioning parathyroid glands has never been described previously. We thus discuss whether there might be a future indication for FCH PET/CT when one such tumour is already known or suspected: to detect a residual or recurrent pituitary adenoma after surgery, to guide surgery or radiotherapy of a meningioma or to localise a hyperfunctioning parathyroid gland. In these potential indications, comparative studies with reference PET tracers or with (99m)Tc-sestaMIBI in case of hyperparathyroidism could be undertaken.

Lung scintigraphy in the diagnosis of pulmonary embolism: current methods and interpretation criteria in clinical practice.

BACKGROUND: In current clinical practice lung scintigraphy is mainly used to exclude pulmonary embolism (PE). Modified diagnostic criteria for planar lung scintigraphy are considered, as newer scitigraphic methods, especially single photon emission computed tomography (SPECT) are becoming more popular. PATIENTS AND METHODS: Data of 98 outpatients who underwent planar ventilation/perfusion (V/Q) scintigraphy and 49 outpatients who underwent V/Q SPECT from the emergency department (ED) were retrospectively collected. Planar V/Q images were interpreted according to 0.5 segment mismatch criteria and revised PIOPED II criteria and perfusion scans according to PISA-PED criteria. V/Q SPECT images were interpreted according to the criteria suggested in EANM guidelines. Final diagnosis of PE was based on the clinical decision of an attending physician and evaluation of a 12 months follow-up period. RESULTS: Using 0.5 segment mismatch criteria and revised PIOPED II, planar V/Q scans were diagnostic in 93% and 84% of cases, respectively. Among the diagnostic planar scans readings specificity for 0.5 segment mismatch criteria was 98%, and 99% for revised PIOPED II criteria. V/Q SPECT showed a sensitivity of 100% and a specificity of 98%, without any non-diagnostic cases. In patients with low pretest probability for PE, planar V/Q scans assessed by 0.5 segment mismatch criteria were diagnostic in 92%, and in 85% using revised PIOPED II criteria, while perfusion scintigraphy without ventilation scans was diagnostic in 80%. CONCLUSIONS: Lung scintigraphy yielded diagnostically definitive results and is reliable in ruling out PE in patients from ED. V/Q SPECT has excellent specificity and sensitivity without any non-diagnostic results. Percentage of non-diagnostic results in planar lung scintigraphy is considerably smaller when 0.5 segment mismatch criteria instead of revised PIOPED II criteria are used. Diagnostic value of perfusion scintigraphy according to PISA-PED criteria is inferior to combined V/Q scintigraphy; the difference is evident especially in patients with low pretest probability for PE.

¹8F-Fluorocholine PET/CT for localization of hyperfunctioning parathyroid tissue in primary hyperparathyroidism: a pilot study.

PURPOSE: Primary hyperparathyroidism is a common endocrine disorder which is diagnosed biochemically and for which therapy is surgical. A prerequisite for minimally invasive surgery, which minimizes morbidity and cost, is accurate localization of the involved gland(s). The aim of this study was to evaluate the usefulness of (18)F-fluorocholine PET/CT for preoperative localization of hyperfunctioning parathyroid tissue. METHODS: (18)F-Fluorocholine PET/CT and conventional parathyroid scintigraphic imaging consisting of (99m)Tc-sestaMIBI SPECT/CT, (99m)Tc-sestaMIBI dual-phase imaging and (99m)Tc-sestaMIBI/pertechnetate subtraction imaging were performed in 24 patients. The diagnostic performance of the imaging methods was compared against histology as the gold standard and postoperative serum Ca(2+) and iPTH values. RESULTS: The sensitivity and specificity of (18)F-fluorocholine PET/CT were 92% and 100%, respectively, in contrast to 49% and 100%, 46% and 100%, and 44% and 100% for (99m)Tc-sestaMIBI SPECT/CT, (99m)Tc-sestaMIBI/pertechnetate subtraction imaging and (99m)Tc-sestaMIBI dual-phase imaging, respectively. Combined conventional scintigraphic imaging had a sensitivity and specificity of 64% and 100%, respectively. The performance of (18)F-fluorocholine PET/CT was superior particularly in patients with multiple lesions or hyperplasia. CONCLUSION: (18)F-Fluorocholine PET/CT appears to be a promising, effective imaging method for localization of hyperfunctioning parathyroid tissue.

Consequence of the introduction of routine FCH PET/CT imaging for patients with prostate cancer: a dual centre survey.

BACKGROUND: Fluorocholine(18F) (FCH) was introduced at the beginning of April 2010 in France, Slovenia and three other EU member states for the localisation of bone metastases of prostate cancer with PET. The aim of the study was to compare the evolution of diagnostic imaging in patients with prostate cancer using a new radiopharmaceutical FCH, observed in France and in Slovenia, and to quantify the consequence of the results of new imaging modality on the detection rate of abnormal metastases and recurrences of prostate cancer. PATIENTS AND METHODS: In two centres (France/Slovenia), a survey of the number of nuclear medicine examinations in patients with prostate cancer was performed, covering 5 quarters of the year since the introduction of FCH. For each examination, the clinical and biological circumstances were recorded, as well as the detection of bone or soft tissue foci. RESULTS: Six hundred and eighty-eight nuclear medicine examinations were performed impatients with prostate cancer. Nuclear medicine examinations were performed for therapy monitoring and follow-up in 23% of cases. The number of FCH PET/CT grew rapidly between the 1(st) and 5(th) period of the observation (+220%), while the number of bone scintigraphies (BS) and fluoride(18F) PET/CTs decreased (-42% and -23% respectively). Fluorodeoxyglucose(18F) (FDG) PET/CT remained limited to few cases of castrate-resistant or metastatic prostate cancer in Paris. The proportion of negative results was significantly lower with FCH PET/CT (14%) than with BS (49%) or fluoride(18F) PET/CT (54%). For bone metastases, the detection rate was similar, but FCH PET/CT was performed on average at lower prostate-specific antigen (PSA) levels and was less frequently doubtful (4% vs. 28% for BS). FCH PET/CT also showed foci in prostatic bed (53% of cases) or in soft tissue (35% of cases). CONCLUSIONS: A rapid development of FCH PET/CT was observed in both centres and led to a higher detection rate of prostate cancer lesions.

Metastatic prostate cancer proven by 18F-FCH PET/CT staging scan in patient with normal PSA but high PSA doubling time.

A 59-year-old man presented with frequent urination. Six months ago, his prostate-specific antigen (PSA) was 1.56 ng/mL; currently it is 3.5 ng/mL (PSA doubling time = 6 months; PSA velocity = 0.19 ng/mL/mo). Biopsy revealed aggressive prostate cancer (Gleason score 5 + 5). Staging with (18)F-fluorocholine PET/CT ((18)F-FCH PET/CT) demonstrated lymph node metastasis. After 6 months of hormonal therapy with goserelin, PSA decreased to 0.38 ng/mL. A (18)F-FCH PET/CT restaging scan demonstrated a global reduction of (18)F-FCH lesion uptake with disappearance of some mediastinal and iliac pelvic lymph node activity.

Radioguided surgery and systemic radionuclide therapy of neuroendocrine tumours.

Neuroendocrine tumours (NETs) may be fatal, though at a significantly slower pace than their exocrine counterparts. Nuclear medicine procedures for diagnosis and treatment of NETs are based on expression of somatostatin receptors. Radioguided surgery is a new method for diagnosing and treating many tumours and uses introperative gamma probes. The use and development of intraoperative gamma probes in the last 10 years has enabled the development of minimally invasive procedures in oncological surgery, with an improvement in both the survival rate and the quality of life. Systemic therapy with radiolabeled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastatic NETs. In terms of tumour regression, the results obtained are encouraging.

99mTc-labelled rituximab, a new non-Hodgkin's lymphoma imaging agent: first clinical experience.

OBJECTIVE: This study was performed to explore the possibility of using Tc-rituximab as an imaging agent to assess expression of CD20 antigen in patients with B-cell non-Hodgkin's lymphoma (NHL) before (radio) immunotherapy, for staging and subsequent evaluation of remission of NHL. METHODS: Rituximab was purified from Mabthera and photoactivated by ultraviolet light. The irradiated solution was aliquoted and labelled with pertechnetate. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity determination and in-vitro stability. Immunoreactivity of Tc-rituximab was assessed on Ramos cells using a direct binding assay. Ten patients (age 31-70 years, mean 50 years) were included, nine with CD20 B-cell NHL and one with CD20-NHL. Whole-body and single photon emission computed tomography images were taken 1, 3, 6 and 20 h postinjection of Tc-rituximab. Scintigraphic results were compared with computerized tomography (CT) findings. RESULTS: In all cases radiochemical purity over 95% was observed with preserved affinity for CD20 antigen. In all patients expected activity was seen in the blood pool, liver, kidneys and spleen. Pathological, moderately to markedly increased Tc-rituximab activity was seen in all but one CT-confirmed NHL involved sites 6 and 20 h postinjection. In one patient, increased activity of Tc-rituximab was additionally seen in one region not seen on CT. In three patients increased accumulation was seen in bone marrow. CONCLUSION: Tc-rituximab is a promising imaging agent suitable for assessing expression of CD20 in patients with NHL before (radio) immunotherapy.

Reproducibility of 99mTc-mercaptoacetyltriglycine renography: population comparison.

PURPOSE: To evaluate reproducibility of diuretic renography, performed according to current guidelines in adult and pediatric patient populations. MATERIALS AND METHODS: Fifty adult and 50 pediatric renograms were processed twice by each of three observers. For differential renal function (DRF) assessment, intraclass correlation coefficient (ICC), standard deviation of DRF calculation and the repeatability parameter were calculated. For drainage assessment, ICC was calculated. Intraobserver and interobserver analysis was performed for both parameters. Patient groups and subgroups (age, DRF asymmetry, drainage) were compared by analysis of variance. RESULTS: Interobserver analysis, adult patient group: DRF-repeatability 4.20%, ICC 0.99. Drainage-ICC 0.92/1.00 (left/right kidney). Pediatric patient group: DRF-repeatability 7.80%, ICC 0.97. Drainage-ICC 0.93/0.85 (left/right kidney). Intraobserver analysis, adult patient group: DRF-repeatability 2.61%, ICC 0.99. Drainage-ICC 0.92/1.00 (left/right kidney). Pediatric patient group: DRF-repeatability 4.76%, ICC 0.98. Drainage-ICC 0.92/0.88 (left/right kidney). Highest repeatability and thus highest DRF dispersion was found in the subgroup of patients with poor/impaired kidney drainage and reduced DRF (repeatability 11.3%, analysis of variance, P<0.001). CONCLUSION: Reproducibility of DRF estimation was excellent in adults in both intraobserver and interobserver analysis. In pediatric patients, intraobserver DRF reproducibility was very good, whereas variation in interobserver analysis was rather high with a potential influence on patient management, but occurred mainly in a subgroup of patients with impaired drainage and ipsilaterally reduced DRF. Drainage assessment was highly reproducible in both patient groups; factors confounding drainage interpretation in discordant patient cases remained unidentified.

Factors influencing radioguided surgery of neuroendocrine tumours using 99mTc-ethylenediamine N,N'-diacetic acid/6-Hydrazinopyridine-3-carboxylic acid-D-Phe1-Tyr3-octreotide.

OBJECTIVE: To determine factors influencing radioguided surgery of neuroendocrine tumours using Tc-ethylenediamine N,N'-diacetic acid/6-Hydrazinopyridine-3-carboxylic acid-D-Phe-Tyr-octreotide and gamma-probe. METHODS: Patients with 17 neuroendocrine tumours were operated on. Three to 6 h before surgery, 550-650 MBq of Tc-labelled octreotide were injected into the patients. Scintigraphy was performed immediately before surgery to confirm uptake of the radiopharmaceutical by the tumour. The uptake was graded on a scale from 0 to 4. Local measurements of radioactivity were performed during surgery using a gamma-probe and small lead shields. RESULTS: Intraoperatively 12 tumours in 11 patients were successfully localized using a gamma-probe: three tumours with uptake grade 4, seven with grade 3 and two with grade 2. Seven tumours were localized in the region of the pancreas, two next to the aortic bifurcation, one in the mesentery and two in the ileocecal region. Tumours were not found in five patients. They were all positive on scintigraphy with tracer uptake grade 4 in one patient, grade 3 in one, and grade 2 in three patients. Localization was confirmed by endoscopic ultrasound, computed tomography and/or MRI. All five tumours were located in the pancreatic area. In four of these patients, tumours were seen in the same localization as preoperatively on follow-up scintigraphy 6-12 months later. CONCLUSION: Factors influencing the success of surgery were high octreotide uptake (grades 3 and 4) and localization of the tumour away from kidneys and spleen. Positive localization on endoscopic ultrasound, computed tomography or MRI, size of tumour, pathohistology and reoperations did not influence surgical success.

Guidelines for direct radionuclide cystography in children.

These guidelines, which summarise the views of the Paediatric Committee of the European Association of Nuclear Medicine, provide a framework which may prove helpful to nuclear medicine teams in daily practice. They contain information on the indications, acquisition, processing and interpretation of direct radioisotope cystography in children. The guidelines should be taken in the context of "good practice" and any local/national rules which apply to nuclear medicine examinations.

Guidelines for radioiodinated MIBG scintigraphy in children.

These guidelines on the use of radioiodinated (99m)Tc-MIBG scintigraphy in children, which summarise the views of the Paediatric Committee of the European Association of Nuclear Medicine, provide a framework which may prove helpful to nuclear medicine teams in daily practice. They have been influenced by the conclusions of the "Consensus Guidelines for MIBG Scintigraphy" (Paris, November 6, 1997) of the European Neuroblastoma Group and by those of the Oncological Committee of the French Society of Nuclear Medicine. The guidelines should be taken in the context of "good practice" and any local/national rules which apply to nuclear medicine examinations.

Sensitivity of ultrasonography in detecting renal parenchymal defects in children.

Renal parenchymal defects (RPD) -- scars, hypoplasia/dysplasia -- in children are a major risk factor for chronic renal failure. Most authors would agree that RPD should be detected and followed by a 99mTc-dimercaptosuccinic acid renal scan (DMSA), as ultrasonography (US) does not seem to be sensitive enough for this purpose. However, it might well be that DMSA is too sensitive and detects RPD that are too small to be clinically significant. The purpose of this study was to evaluate the sensitivity of US in identifying patients with clinically significant RPD and in detecting RPD of various grades as seen by DMSA. In 89 children with abnormal DMSA, a second DMSA, US, and other tests for evaluating renal function were performed at least 1 year after the first DMSA. The extent of RPD detected by DMSA and US was correlated with renal function parameters. In all 5 patients with diminished renal function, RPD were detected by both DMSA scan and US. In addition, US detected clinically insignificant RPD in 48 of 67 cases (71.6%). The present study has shown that, compared with DMSA, US is sensitive enough to detect clinically significant RPD in children. The substitution of DMSA with US would be beneficial, as this would eliminate radiation exposure, reduce costs, and increase availability.