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Purpose: Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with 99mTc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Methods: Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with 99mTc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of 99mTc-rituximab. Results: On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80°C for 195 days. The direct binding assay showed preserved ability of 99mTc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound 99mTc-rituximab being internalised over 4 h at 37°C. Conclusion: Our results demonstrate that 99mTc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. 99mTc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. [ABSTRACT FROM AUTHOR]

A generator of the harmonic signal is described for frequencies in the acoustic region with the reference stabilized amplitude, linear frequency scale and total harmonic distortion below 2 10. The signal is produced as the solution of the corresponding differential equation where the constant amplitude is maintained by periodic control of the first derivative value x(t) at the moments when x(t) crosses zero and has a positive slope. [ABSTRACT FROM AUTHOR]

Background. Positron emission tomography-computed tomography (PET/CT) with 18F-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.

Hybrid imaging combining PET and CT is standard technique already for many years. Now it is becoming state of the art nuclear medicine technique also in the field of single photon emission tomography (SPECT) as SPECT/CT. Advantages of hybrid imaging are improved quality of the images using CT data for attenuation correction based on true transmission density data in the individual patient, and CT and SPECT fusion images providing accurate localisation of the tracer uptake. The former is useful in dosimetric calculation in case of tumours treated by radiopharmaceuticals emitting also gamma photons such as 177-Lu. Accurate localisation of increased tracer uptake is important especially in the diagnostic of tumours. This can improve specificity of tumour imaging, for example differentiation between abnormal uptake in the primary tumour and uptake in the metastasis in a lymph node. In this respect hybrid imaging can improve the accuracy of staging and evaluation of treatment follow-up. In several areas single photon emitting radiopharmaceuticals need to be used since there are no useful PET tracers available. This is true in case of neuroendocrine tumours, adrenal tumours, atypical haemangiomas etc., and also in case of benign parathyroid adenomas or osteoid osteomas when radioguided surgery using gamma probe is considered. Lymphoscintigraphy for radioguided sentinel node scintigraphy has become standard in various types of cancers. If exact localisation of the sentinel node can be shown on a fused image this is certainly a big help for the surgeon performing biopsy. The ability of SPECT/CT to improve diagnostic accuracy, especially specificity has great potential in further grow of nuclear medicine techniques in evaluation of tumours.

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.

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.

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)., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

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.

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.

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.

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.

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.

Neuroendocrine tumours (NETs) are rare pathologies which origin from neuroectodermic and endodermic cells and that can produce peptides and amino acids. About 70% of NETs derive from gastroenterohepatic (GEP) system and the other 30% from the different sites through the body. They are distinguished into single and multiple localizations and also into sporadic, familial multiple endocrine-related forms and recurrent forms. Moreover, when they produce hormones they usually are symptomatic; yet, they are characterized by the synthesis and secretion in the blood stream of several tumor-specific markers or can express somatostatin receptors in their cellular surface. The diagnosis and follow-up of NETs rely on laboratory studies, histopathology and the combination of anatomical and functional imaging, with the latter being the main method for monitoring response to therapy. In recent years, nuclear medicine has contributed to the impressive development of the knowledge of NETs in terms of biology (receptor scintigraphy), pharmacology (development of new tracers) and therapy (radiometabolic therapy). Nuclear medicine procedures for diagnosis and treatment of NETs are based on the biological properties of these tumours: the expression of somatostatin receptors. Somatostatin receptor scintigraphy not only has a crucial role in diagnosis and staging of NETs, but also in assessing suitability for treatment with cold and radiolabelled somatostatin analogues, as well as in monitoring response to treatment and detecting recurrent disease. In conventional nuclear medicine, the two most important functional imaging modalities are ¹¹¹In-octrescan and ¹²³I-MIBG. Over the last 5 years, due to the development of new tracers, such as ⁶⁸Ga labelled-DOTA-peptides PET and ¹⁸F-DOPA, PET has also been employed with significant benefits in the diagnosis and management of NETs.

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.

Aim: The aim of this study was to analyze the influence of scintigraphic uptake grade and tumour size on radio-guided surgery of neuroendocrine tumours (NETs) using 99mTc-EDDA/HYNIC-TOC (99mTc-octreotide)., Methods: We investigated 21 patients with NET (F=8, M=13) for localization of 27 known lesions using a gamma probe. Three to 6 hours before surgery, 550-650 MBq of 99mTc-octreotide was injected followed by immediate imaging prior to surgery. The uptake was graded on a scale from 0-4. Localization was confirmed by endoscopic ultrasound (EUS), computed tomography (CT) and/or magnetic resonance imaging (MRI). Morphological images were used to determine size of the lesion. Local measurements of radioactivity were performed during surgery using a gamma probe., Results: Twenty lesions were successfully localized intraoperatively using a gamma probe (7=grade 4, 9=grade 3, 2=grade 2 and 2=grade 0). The size of successfully localized lesions ranged between 9 and 50 mm. Seven lesions were not localized successfully of which 6 were seen on scintigraphy (2=grade 4, 1=grade 3 and 3=grade 2). The 7th lesion was not seen on preoperative scintigraphy and not localized successfully. The size of unsuccessfully localized lesions ranged between 7 and 30 mm., Conclusions: High octreotide uptake (grade 3 and 4) influence radioguided surgery. Tumour size did not influence the success of localization of lesions by gamma probe.