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Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson’s disease. The caudate–putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D2/D3 receptor (D2/D3R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [18F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection. Male Wistar rats were assigned to three different groups: controls, sham-injected hemi-PD rats, and BoNT-A-injected hemi-PD rats. Disease-specific motor impairment was verified by apomorphine and amphetamine rotation testing. Animal-specific magnetic resonance imaging was performed for co-registration and anatomical reference. PET quantification was achieved using PMOD software with the simplified reference tissue model 2. Hemi-PD rats exhibited a constant increase of 23% in D2/D3R availability in the CPu, which was almost normalized by intrastriatal application of BoNT-A. Importantly, the BoNT-A effect on striatal D2/D3R significantly correlated with behavioral results in the apomorphine rotation test. Our results suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing interhemispheric changes of striatal D2/D3R. [ABSTRACT FROM AUTHOR]

Purpose: From 2010 until July 2016, the EANM Research Ltd. (EARL) FDG-PET/CT accreditation program has collected over 2500 phantom datasets from approximately 200 systems and 150 imaging sites worldwide. The objective of this study is to report the findings and impact of the accreditation program on the participating PET/CT systems. Methods: To obtain and maintain EARL accredited status, sites were required to complete and submit two phantom scans - calibration quality control (CalQC), using a uniform cylindrical phantom and image quality control (IQQC), using a NEMA NU2-2007 body phantom. Average volumetric SUV bias and SUV recovery coefficients (RC) were calculated and the data evaluated on the basis of quality control (QC) type, approval status, PET/CT system manufacturer and submission order. Results: SUV bias in 5% ( n = 96) of all CalQC submissions ( n = 1816) exceeded 10%. After corrective actions following EARL feedback, sites achieved 100% compliance within EARL specifications. 30% ( n = 1381) of SUVmean and 23% ( n = 1095) of SUVmax sphere recoveries from IQQC submissions failed to meet EARL accreditation criteria while after accreditation, failure rate decreased to 12% ( n = 360) and 9% ( n = 254), respectively. Most systems demonstrated longitudinal SUV bias reproducibility within ±5%, while RC values remained stable and generally within ±10% for the four largest and ±20% for the two smallest spheres. Conclusions: Regardless of manufacturer or model, all investigated systems are able to comply with the EARL specifications. Within the EARL accreditation program, gross PET/CT calibration errors are successfully identified and longitudinal variability in PET/CT performances reduced. The program demonstrates that a harmonising accreditation procedure is feasible and achievable. [ABSTRACT FROM AUTHOR]

Olfactory deficits occur as early non-motor symptoms of idiopathic Parkinson's disease (PD) in humans. The first central relay of the olfactory pathway, the olfactory bulb (OB), depends, among other things, on an intact, functional crosstalk between dopaminergic interneurons and dopamine receptors (D2/D3R). In rats, hemiparkinsonism (hemi-PD) can be induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB), disrupting dopaminergic neurons of the substantia nigra pars compacta (SNpc). In a previous study, we showed that subsequent injection of botulinum neurotoxin-A (BoNT-A) into the striatum can reverse most of the pathological motor symptoms and normalize the D2/D3R availability. To determine whether this rat model is suitable to explain olfactory deficits that occur in humans with PD, we examined the availability of D2/D3R by longitudinal [18F]fallypride-PET/CT, the density of tyrosine hydroxylase immunoreactivity in the OB, olfactory performance by an orienting odor identification test adapted for rats, and a connectome analysis. PET/CT and immunohistochemical data remained largely unchanged after 6-OHDA lesion in experimental animals, suggesting that outcomes of the 6-OHDA hemi-PD rat model do not completely explain olfactory deficits in humans. However, after subsequent ipsilateral BoNT-A injection into the striatum, a significant 8.5% increase of the D2/D3R availability in the ipsilateral OB and concomitant improvement of olfactory performance were detectable. Based on tract-tracing meta-analysis, we speculate that this may be due to indirect connections between the striatum and the OB. [ABSTRACT FROM AUTHOR]

Abstract: Background: Current imaging techniques are of limited value for lymph node (LN) staging in bladder cancer (BCa) patients scheduled for radical cystectomy (RC). Objective: Evaluate the diagnostic efficacy of [11C]choline positron emission tomography in combination with computed tomography (PET/CT) for LN staging of patients with BCa scheduled for RC and compare that efficacy with the diagnostic efficacy of CT and the gold standard of histopathologic evaluation. Design, setting, and participants: From June 2004 to May 2007, 44 patients with localized BCa were staged with [11C]choline PET with low-dose CT for attenuation correction and simultaneous intravenous and rectal contrast-enhanced diagnostic CT before RC and pelvic lymph node dissection (PLND). LNs were dissected from the internal and external iliac arteries up to the origin of the inferior mesentery artery according to a template with 14 predefined anatomic fields. Intervention: Diagnostic [11C]choline PET/CT before RC and regional LN dissection. Measurements: Histopathologic findings of resected LN were correlated with the results of [11C]choline PET/CT and CT alone in a patient- and field-based manner. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [11C]choline PET/CT and CT were assessed. Results and limitations: LN metastases were found in 12 of 44 patients (27%). On patient-based analysis, sensitivity, specificity, PPV, NPV, and accuracy for [11C]choline PET/CT were calculated as 58%, 66%, 39%, 81%, and 64%, respectively; and for CT the calculated percentages were 75%, 56%, 39%, 86%, and 61%, respectively. Twenty-five of 471 dissected LN fields (5%) showed metastases. On field-based analysis, sensitivity, specificity, PPV, NPV, and accuracy for [11C]choline PET/CT were 28%, 95%, 21%, 96%, and 91%, respectively; for CT, the calculated percentages were 39%, 92%, 20%, 96%, and 90%, respectively. Limitations of this study are small patient number and the fact that not all patients underwent extensive PLND. Conclusions: In patients with BCa who were scheduled for RC, preoperative LN staging with [11C]choline PET/CT was not able to improve diagnostic efficacy compared with conventional CT alone. [Copyright &y& Elsevier]

Abstract: Context: Choline positron emission tomography (PET)/computed tomography (CT) is a currently used diagnostic tool in restaging prostate cancer (PCa) patients with increasing prostate-specific antigen (PSA) after either radical prostatectomy (RP) or external-beam radiation therapy (EBRT). However, no final recommendations have been made on the use of this modality for patient management. Objective: To critically analyse the current evidence for the use of choline PET/CT scanning in the management of patients with a progressive increase in PSA after radical treatment for PCa, evaluating its diagnostic accuracy in the detection of recurrences, the clinical predictors of positive PET/CT examinations, and the modalities’ role as a guide for tailored therapeutic strategies. Evidence acquisition: Data on recently published (2003–2010) original articles, review articles, and editorials concerning the role of choline PET/CT in this scenario were analysed. Evidence synthesis: The diagnostic accuracy of choline PET in detecting sites of PCa relapse has been investigated by several authors, and the overall reported sensitivity ranges between 38% and 98%. It has been demonstrated that choline PET technology''s positive detection rate improves with increasing PSA values. The routine use of choline PET/CT cannot be recommended for PSA values <1ng/ml. However, in addition to PSA serum value, PSA doubling time (PSA DT), and other clinical and pathologic features—including locally advanced tumour (pT3b–T4) or lymph node involvement at initial staging—should be considered to refer patients to choline PET/CT study. Choline PET/CT may be also proposed as a image guide either for experimental surgical or radiation therapy treatments. Conclusions: According to the current available data, choline PET/CT plays a role in the management of biochemical relapse. Its accuracy is correlated to PSA value, PSA DT, and other pathologic features. Choline PET/CT may be proposed as a guide for individualised treatment of recurrence. [Copyright &y& Elsevier]

Abstract: Introduction: To evaluate [11C]Choline positron emission tomography (PET)/computed tomography (CT) for staging and restaging of patients with advanced prostate cancer and to compare the diagnostic performance of PET, CT and PET/CT. Methods: Forty-five consecutive patients with advanced prostate cancer underwent [11C]Choline-PET/CT between 5/2004 and 2/2006. Results: Overall, 295 lesions were detected: PET alone, 178 lesions; diagnostic CT, 221 lesions; PET/CT (low-dose CT), 272 lesions; PET/CT (diagnostic CT), 295 lesions. Two thirds of the lesions were located in the bone; one third in the prostate, lymph nodes, periprostatic tissue and soft tissue (lung, liver). The use of diagnostic CT did not result in a statistically significant difference with respect to lesion localization certainty and lesion characterization (P=.063, P=.063). PET-negative but PET/CT-positive lesions were mostly localized in the bone (78%, 91/117) as were PET-positive and CT-negative lesions (72%, 53/74). Of the latter, 91% (48/53) represented bone marrow and 9% (5/53) cortical involvement. Conclusions: Staging and restaging with [11C]Choline PET/CT in patients with advanced prostate cancer improve the assessment of local and regional recurrent as well as metastatic disease including skeletal manifestations. [11C]Choline PET/CT (with a low-dose CT) results in improved localization and lesion characterization. [11C]Choline PET/CT provides an added value for skeletal manifestations. [11C]Choline PET/CT changed disease management in 11 (24%) of 45 patients with advanced prostate cancer. [Copyright &y& Elsevier]