Differences in cause and 12-month follow-up outcome of parkinsonian symptoms in depressed older adults treated with antipsychotics: a case series.

BACKGROUND: Parkinsonian symptoms are common adverse effects of antipsychotics. Older adults are particularly vulnerable to drug-induced parkinsonism. Nonetheless, parkinsonian symptoms in seniors treated with antipsychotics cannot be straightforwardly attributed to antipsychotic medication. A comprehensive diagnostic workup is necessary in many cases in order to shed light on the cause of such symptoms in this patient population. CASE SERIES: Eight cases of hospitalized depressed older adults with parkinsonian symptoms, who were treated for at least one year with antipsychotics, are reported. Based on neurological consultation, structural brain imaging and Ioflupane (I-123) dopamine transporter (DAT) single photon emission computerized tomography (SPECT), Parkinson's disease was diagnosed in one case, idiopathic tremor in another, vascular parkinsonism in another one, while in another individual parkinsonian symptoms persisted at 12-month post-discharge follow-up even though his/her symptoms were classified as drug-induced on discharge. In four patients, parkinsonian symptoms were definitely drug-induced and no movement disturbances were reported at follow-up. CONCLUSIONS: Differences in the cause and outcome of parkinsonian symptoms in seniors treated with antipsychotics merit systematic and in-depth study considering the therapeutic and prognostic implications of an accurate detection of the cause of such symptoms. Familiarizing clinical psychiatrists with these differences could pave the way towards approaching seniors with severe, atypical and/or persistent parkinsonian symptoms in a more individualized diagnostic and therapeutic manner, and towards more cautious prescribing of antipsychotics in this age group.

Prospective head-to-head comparison of 11C-choline-PET/MR and 11C-choline-PET/CT for restaging of biochemical recurrent prostate cancer.

PURPOSE: Whole-body integrated 11C-choline PET/MR might provide advantages compared to 11C-choline PET/CT for restaging of prostate cancer (PC) due to the high soft-tissue contrast and the use of multiparametric MRI, especially for detection of local recurrence and bone metastases. MATERIALS AND METHODS: Ninety-four patients with recurrent PC underwent a single-injection/dual-imaging protocol with contrast-enhanced PET/CT followed by fully diagnostic PET/MR. Imaging datasets were read separately by two reader teams (team 1 and 2) assessing the presence of local recurrence, lymph node and bone metastases in predefined regions using a five-point scale. Detection rates were calculated. The diagnostic performance of PET/CT vs. PET/MR was compared using ROC analysis. Inter-observer and inter-modality variability, radiation exposure, and mean imaging time were evaluated. Clinical follow-up, imaging, and/or histopathology served as standard of reference (SOR). RESULTS: Seventy-five patients qualified for the final image analysis. A total of 188 regions were regarded as positive: local recurrence in 37 patients, 87 regions with lymph node metastases, and 64 regions with bone metastases. Mean detection rate between both readers teams for PET/MR was 84.7% compared to 77.3% for PET/CT (p > 0.05). Local recurrence was identified significantly more often in PET/MR compared to PET/CT by team 1. Lymph node and bone metastases were identified significantly more often in PET/CT compared to PET/MR by both teams. However, this difference was not present in the subgroup of patients with PSA values ≤2 ng/ml. Inter-modality and inter-observer agreement (K > 0.6) was moderate to substantial for nearly all categories. Mean reduction of radiation exposure for PET/MR compared to PET/CT was 79.7% (range, 72.6-86.2%). Mean imaging time for PET/CT was substantially lower (18.4 ± 0.7 min) compared to PET/MR (50.4 ± 7.9 min). CONCLUSIONS: 11C-choline PET/MR is a robust imaging modality for restaging biochemical recurrent PC and interpretations between different readers are consistent. It provides a higher diagnostic value for detecting local recurrence compared to PET/CT with the advantage of substantial dose reduction. Drawbacks of PET/MR are a substantially longer imaging time and a slight inferiority in detecting bone and lymph node metastases in patients with PSA values >2 ng/ml. Thus, we suggest the use of 11C-choline PET/MR especially for patients with low (≤2 ng/ml) PSA values, whereas PET/CT is preferable in the subgroup with higher PSA values.

Diagnostic Efficacy of (68)Gallium-PSMA Positron Emission Tomography Compared to Conventional Imaging for Lymph Node Staging of 130 Consecutive Patients with Intermediate to High Risk Prostate Cancer.

PURPOSE: Current standard imaging techniques are insufficient to reliably detect lymph node metastases in prostate cancer. Recently ligands of PSMA (prostate specific membrane antigen) were introduced in PET (positron emission tomography) of prostate cancer. Thus the aims of this retrospective analysis were to 1) investigate the diagnostic efficacy of (68)Ga-PSMA-PET imaging for lymph node staging in patients with prostate cancer scheduled for radical prostatectomy and 2) compare it to morphological imaging (computerized tomography and magnetic resonance tomography) with histopathological evaluation as the standard of reference. MATERIALS AND METHODS: A total of 130 patients with intermediate to high risk prostate cancer were staged with (68)Ga-PSMA-PET/magnetic resonance tomography or PET/computerized tomography from December 2012 to November 2014 before radical prostatectomy and template pelvic lymph node dissection. Histopathological findings of resected tissue were statistically correlated with the results of (68)Ga-PSMA-PET and morphological imaging in a patient and template based manner. RESULTS: Lymph node metastases were found in 41 of 130 patients (31.5%). On patient based analysis the sensitivity, specificity and accuracy of (68)Ga-PSMA-PET were 65.9%, 98.9% and 88.5%, and those of morphological imaging were 43.9%, 85.4% and 72.3%, respectively. Of 734 dissected lymph node templates 117 (15.9%) showed metastases. On template based analysis the sensitivity, specificity and accuracy of (68)Ga-PSMA-PET were 68.3%, 99.1% and 95.2%, and those of morphological imaging were 27.3%, 97.1% and 87.6%, respectively. On ROC analysis (68)Ga-PSMA-PET performed significantly better than morphological imaging alone on patient and template based analyses (p = 0.002 and <0.001, respectively). CONCLUSIONS: In patients with intermediate to high risk prostate cancer preoperative lymph node staging with (68)Ga-PSMA-PET proved to be superior to standard routine imaging. Thus it has the potential to replace current standard imaging for this indication if confirmed by prospective studies.

Categorical versus continuous circulating tumor cell enumeration as early surrogate marker for therapy response and prognosis during docetaxel therapy in metastatic prostate cancer patients.

BACKGROUND: Circulating tumor cell (CTCs) counts might serve as early surrogate marker for treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) patients. We prospectively assessed categorical and continuous CTC-counts for their utility in early prediction of radiographic response, progression-free (PFS) and overall survival (OS) in mCRPC patients treated with docetaxel. METHODS: CTC-counts were assessed in 122 serial samples, as continuous or categorical (<5 vs. ≥5 CTCs) variables, at baseline (q0) and after 1 (q1), 4 (q4) and 10 (q10) cycles of docetaxel (3-weekly, 75 mg/m2) in 33 mCRPC patients. Treatment response (TR) was defined as non-progressive (non-PD) and progressive disease (PD), by morphologic RECIST or clinical criteria at q4 and q10. Binary logistic and Cox proportional hazards regression analyses were used as statistical methods. RESULTS: Categorical CTC-count status predicted PD at q4 already after one cycle (q1) and after 4 cycles (q4) of chemotherapy with an odds ratio (OR) of 14.9 (p=0.02) and 18.0 (p=0.01). Continuous CTC-values predicted PD only at q4 (OR 1.04, p=0.048). Regarding PFS, categorical CTC-counts at q1 were independent prognostic markers with a hazard ratio (HR) of 3.85 (95% CI 1.1-13.8, p=0.04) whereas early continuous CTC-values at q1 failed significance (HR 1.02, 95% CI 0.99-1.05, p=0.14). For OS early categorical and continuous CTC-counts were independent prognostic markers at q1 with a HR of 3.0 (95% CI 1.6-15.7, p=0.007) and 1.02 (95% CI 1.0-1.040, p=0.04). CONCLUSIONS: Categorical CTC-count status is an early independent predictor for TR, PFS and OS only 3 weeks following treatment initiation with docetaxel whereas continuous CTC-counts were an inconsistent surrogate marker in mCRPC patients. For clinical practice, categorical CTC-counts may provide complementary information towards individualized treatment strategies with early prediction of treatment efficacy and optimized sequential treatment.

Detection of liver metastases in patients with adenocarcinomas of the gastrointestinal tract: comparison of (18)F-FDG PET/CT and MR imaging.

PURPOSE: Aim of our study was to compare the diagnostic performance of (18)F-FDG PET/CT and MR imaging (MRI) in the detection of liver metastases in patients with adenocarcinomas of the gastrointestinal tract. METHODS: A total of 49 patients with adenocarcinomas of the gastrointestinal tract who had undergone (18)F-FDG PET/CT and MRI of the liver were included in this study. The MRI protocol included diffusion-weighted imaging and dynamic contrast-enhanced MR imaging after intravenous injection of Gd-DTPA. PET and MR images were analyzed by two experienced radiologists. Imaging results were correlated with histopathological findings or imaging follow-up as available. Sensitivities of both modalities were compared using McNemar Test. Receiver operating characteristic (ROC) curves were calculated to determine the diagnostic performance in correctly identifying liver metastases. RESULTS: A total of 151 metastases were confirmed. For lesion detection, MRI was significantly superior to (18)F-FDG PET/CT. Sensitivity of MRI in detecting metastases was 86.8% for Reader 1 (R1) and 87.4% for Reader 2 (R2), of PET/CT 66.2% for R1 and 68.2% for R2. Regarding only metastases with diameters of 10 mm or less, sensitivities of MRI were 66.7% for R1 and 75.0% for R2, and were significantly higher than those of PET/CT (17.9% for R1 and 20.5% for R2). ROC analysis showed superiority for lesion classification of MRI as compared to (18)F-FDG PET/CT. CONCLUSION: MRI is significantly superior to (18)F-FDG PET/CT in the detection and classification of liver metastases in patients with adenocarcinomas of the gastrointestinal tract, especially in the detection of small metastases.

11C-Choline PET/pathology image coregistration in primary localized prostate cancer.

PURPOSE: The aim of this study was to develop a methodology for the comparison of pathology specimens after prostatectomy (post-S) with PET images obtained before surgery (pre-S). This method was used to evaluate the merit of (11)C-choline PET/CT for delineation of gross tumour volume (GTV) in prostate cancer (PC). METHODS: In 28 PC patients, (11)C-choline PET/CT was performed before surgery. PET/CT data were coregistered with the pathology specimens. GTV on PET images (GTV-PET) was outlined automatically and corrected manually. Tumour volume in the prostate (TVP) was delineated manually on the pathology specimens. Based on the coregistered PET/pathology images, the following parameters were assessed: SUVmax and SUVmean in the tumoral and nontumoral prostate (NP), GTV-PET (millilitres) and TVP (millilitres). RESULTS: PET/pathology image coregistration was satisfactory. Mean SUVmax in the TVP was lower than in the NP: 5.0 and 5.5, respectively (p = 0.093). Considering the entire prostate, SUVmax was located in the TVP in two patients, in the TVP and NP in 12 patients and exclusively in NP in 14 patients. Partial overlap the TVP and GTV-PET was seen in 71% of patients, and complete overlap in 4%. CONCLUSION: PET/pathology image coregistration can be used for evaluation of different imaging modalities. (11)C-Choline PET failed to distinguish tumour from nontumour tissue.

Prospective comparison of computed tomography, diffusion-weighted magnetic resonance imaging and [11C]choline positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer patients.

PURPOSE: The aim of this study was to prospectively compare diffusion-weighted magnetic resonance imaging (DWI) and [(11)C]choline positron emission tomography/computed tomography (PET/CT) with computed tomography (CT) for preoperative lymph node (LN) staging in prostate cancer (PCa) patients. METHODS: Between June 2010 and May 2012, CT, DWI and [(11)C]choline PET/CT were performed preoperatively in 33 intermediate- and high-risk PCa patients undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) including obturator fossa and internal, external and common iliac fields. Patient- and field-based performance characteristics for all three imaging techniques based on histopathological results are reported. Imaging techniques were compared by means of the area under the curve (AUC). RESULTS: LN metastases were detected in 92 of 1,012 (9%) LNs from 14 of 33 (42%) patients. On patient-based analysis, sensitivity, specificity and accuracy for CT were 57, 68 and 64%, respectively, for DWI were 57, 79 and 70%, respectively, and for [(11)C]choline PET/CT were 57, 90 and 76%, respectively. On field-based analysis, these numbers for CT were 47, 94 and 88%, respectively, for DWI were 56, 97 and 92%, respectively, and for [(11)C]choline PET/CT were 62, 96 and 92%, respectively. Neither DWI nor [(11)C]choline PET/CT performed significantly better than CT on pairwise comparison of patient- and field-based results. CONCLUSION: All three imaging techniques exhibit a rather low sensitivity with less than two thirds of LN metastases being detected on patient- and field-based analysis. Overall diagnostic efficacy did not differ significantly between imaging techniques, whereas distinct performance characteristics, esp. patient-based specificity, were best for [(11)C]choline PET/CT followed by DWI and CT.

Diagnostic value of retrospective PET-MRI fusion in head-and-neck cancer.

BACKGROUND: To assess the diagnostic value of retrospective PET-MRI fusion and to compare the results with side-by-side analysis and single modality use of PET and of MRI alone for locoregional tumour and nodal staging of head-and-neck cancer. METHODS: Thirty-three patients with head-and-neck cancer underwent preoperative contrast-enhanced MRI and PET/CT for staging. The diagnostic data of MRI, PET, side-by-side analysis of MRI and PET images and retrospective PET-MRI fusion were systematically analysed for tumour and lymph node staging using receiver operating characteristic (ROC) analysis. The results were correlated to the histopathological evaluation. RESULTS: The overall sensitivity/specificity for tumour staging for MRI, PET, side-by-side analysis and retrospective PET-MRI fusion was 79%/66%, 82%/100%, 86%/100% and 89%/100%, respectively. The overall sensitivity/specificity for nodal staging on a patient basis for MRI, PET, side-by-side analysis and PET-MRI fusion was 94%/64%, 94%/91%, 94%/82% and 94%/82%, respectively. MRI, PET, side-by-side analysis and retrospective image fusion were associated with correct diagnosis/over-staging/under-staging of N-staging in 70.4%/18.5%/11.1%, 81.5%/7.4%/11.1%, 81.5%/11.1%/7.4% and 81.5%/11.1%/7.4%, respectively.ROC analysis showed no significant differences in tumor detection between the investigated methods. The Area Under the Curve (AUC) for MRI, PET, side-by-side analysis and retrospective PET-MRI fusion were 0.667/0.667/0.702/0.708 (p > 0.05). The most reliable technique in detection of cervical lymph node metastases was PET imaging (AUC: 0.95), followed by side-by-side analysis and retrospective image fusion technique (AUC: 0.941), which however, was not significantly better then the MRI (AUC 0.935; p > 0.05). CONCLUSIONS: We found a beneficial use of multimodal imaging, compared with MRI or PET imaging alone, particular in individual cases of recurrent tumour disease. Side-by-side analysis and retrospective image fusion analysis did not perform significantly differently.

Preoperative lymph node staging in patients with primary prostate cancer: comparison and correlation of quantitative imaging parameters in diffusion-weighted imaging and 11C-choline PET/CT.

PURPOSE: To compare the diagnostic performance of DWI and 11C-choline PET/CT in the assessment of preoperative lymph node status in patients with primary prostate cancer. MATERIAL AND METHODS: Thirty-three patients underwent DWI and 11C-choline PET/CT prior to prostatectomy and extended pelvic lymph node dissection. Mean standardised uptake value (SUV(mean)) and mean apparent diffusion coefficient (ADC) of 76 identified lymph nodes (LN) were measured and correlated with histopathology. ADC values and SUVs were compared using linear regression analysis. RESULTS: A significant difference between benign and malignant LN was observed for ADC values (1.17 vs. 0.96 × 10(-3) mm(2)/s; P < 0.001) and SUV(mean) (1.61 vs. 3.20; P < 0.001). ROC analysis revealed an optimal ADC threshold of 1.01 × 10(-3) mm(2)/s for differentiating benign from malignant LN with corresponding sensitivity/specificity of 69.70%/78.57% and an area under the curve (AUC) of 0.785. The optimal threshold for SUV(mean) was 2.5 with corresponding sensitivity/specificity of 69.72%/90.48% and with an AUC of 0.832. ADC values and SUV(mean) showed a moderate significant inverse correlation (r = -0.63). CONCLUSION: Both modalities reveal similar moderate diagnostic performance for preoperative lymph node staging of prostate cancer, not justifying their application in routine clinical practice at this time. The only moderate inverse correlation between ADC values and SUV(mean) suggests that both imaging parameters might provide complementary information on tumour biology. KEY POINTS: • Conventional imaging shows low performance for lymph node staging in prostate cancer. • DWI and 11C-choline PET/CT both provide additional functional information • Both functional modalities reveal only moderate diagnostic performance.

Prognostic value of 11C-choline PET/CT and CT for predicting survival of bladder cancer patients treated with radical cystectomy.

BACKGROUND: In patients with bladder cancer (BCa) preoperative staging with (11)C-choline positron emission tomography-computed tomography (PET/CT) could be used to derive prognostic information and hence stratify patients preoperatively with respect to disease management. METHODS: From June 2004 to May 2007, 44 patients with localized BCa were staged with (11)C-choline PET/CT before radical cystectomy. The results of imaging were correlated to overall survival (OS) and cumulative incidence of cancer-specific death (CSD). RESULTS: There was no statistically significant difference in OS and CSD between the patient groups when stratified for organ-confined versus non-organ-confined disease or lymph node involvement defined by either (11)C-choline PET/CT (OS: p = 0.262, hazard ratio [HR] = 1.60; p = 0.527, HR = 0.76; CSD: p = 0.144, HR = 2.25; p = 0.976, HR = 0.98) or CT (OS: p = 0.518, HR = 1.34; p = 0.228, HR = 1.67; CSD: p = 0.323, HR = 1.90; p = 0.136, HR = 2.38). The limitation of this study is the small number of included patients. CONCLUSION: In our prospective trial neither CT nor (11)C-choline PET/CT were able to sufficiently predict OS or CSD in BCa patients treated with radical cystectomy albeit trends and moderately increased HRs could be demonstrated without significant differences between CT or (11)C-choline PET/CT. However, these trends might prove statistically significant in bigger patient cohorts. Therefore initial transsectional imaging might be of clinical relevance in respect to prognosis and could play a role in the counseling of BCa patients.

PET/MR in prostate cancer: technical aspects and potential diagnostic value.

PET/MR is a new multimodal imaging technique that is expected to improve diagnostic performance of imaging in conditions in which assessment of changes in soft tissue is important such as prostate cancer. Despite substantial changes in PET technology compared to PET/CT, initial studies have demonstrated that integrated PET/MR provides comparable image quality to that of PET/CT, retaining PET quantification efficacy. In this review we briefly describe technological changes compared to PET/CT that made integrated PET/MR possible, propose acquisition protocols for evaluation of prostate cancer with this new multimodal approach, present initial results concerning the application of PET/MR in prostate cancer, and outline the potential for further clinical applications, focusing on potential incremental value compared to present diagnostic performance.

Tumour volume delineation in prostate cancer assessed by [11C]choline PET/CT: validation with surgical specimens.

PURPOSE: PET has been proven to be helpful in the delineation of gross tumour volume (GTV) for external radiation therapy in several tumour entities. The aim of this study was to determine if [(11)C]choline PET could be used to localize the carcinomatous tissue within the prostate in order to specifically target this area for example with high-precision radiation therapy. METHODS: Included in this prospective study were 20 patients with histological proven prostate carcinoma who underwent [(11)C]choline PET/CT before radical prostatectomy. After surgical resection, specimens were fixed and cut into 5-mm step sections. In each section the area of the carcinoma was delineated manually by an experienced pathologist and digitalized, and the histopathological tumour volume was calculated. Shrinkage due to resection and fixation was corrected using in-vivo and ex-vivo CT data of the prostate. Histopathological tumour location and size were compared with the choline PET data. Different segmentation algorithms were applied to the PET data to segment the intraprostatic lesion volume. RESULTS: A total of 28 carcinomatous lesions were identified on histopathology. Only 13 (46 %) of these lesions had corresponding focal choline uptake. In the remaining lesions, no PET uptake (2 lesions) or diffuse uptake not corresponding to the area of the carcinoma (13 lesions) was found. In the patients with corresponding PET lesions, no suitable SUV threshold (neither absolute nor relative) was found for GTV segmentation to fit the volume to the histological tumour volume. CONCLUSION: The choline uptake pattern corresponded to the histological localization of prostate cancer in fewer than 50 % of lesions. Even when corresponding visual choline uptake was found, this uptake was highly variable between patients. Therefore SUV thresholding with standard algorithms did not lead to satisfying results with respect to defining tumour tissue in the prostate.

Comparison of integrated whole-body [11C]choline PET/MR with PET/CT in patients with prostate cancer.

PURPOSE: To evaluate the performance of conventional [(11)C]choline PET/CT in comparison to that of simultaneous whole-body PET/MR. METHODS: The study population comprised 32 patients with prostate cancer who underwent a single-injection dual-imaging protocol with PET/CT and subsequent PET/MR. PET/CT scans were performed applying standard clinical protocols (5 min after injection of 793 ± 69 MBq [(11)C]choline, 3 min per bed position, intravenous contrast agent). Subsequently (52 ± 15 min after injection) PET/MR was performed (4 min per bed position). PET images were reconstructed iteratively (OSEM 3D), scatter and attenuation correction of emission data and regional allocation of [(11)C]choline foci were performed using CT data for PET/CT and segmented Dixon MR, T1 and T2 sequences for PET/MR. Image quality of the respective PET scans and PET alignment with the respective morphological imaging modality were compared using a four point scale (0-3). Furthermore, number, location and conspicuity of the detected lesions were evaluated. SUVs for suspicious lesions, lung, liver, spleen, vertebral bone and muscle were compared. RESULTS: Overall 80 lesions were scored visually in 29 of the 32 patients. There was no significant difference between the two PET scans concerning number or conspicuity of the detected lesions (p not significant). PET/MR with T1 and T2 sequences performed better than PET/CT in anatomical allocation of lesions (2.87 ± 0.3 vs. 2.72 ± 0.5; p = 0.005). The quality of PET/CT images (2.97 ± 0.2) was better than that of the respective PET scan of the PET/MR (2.69 ± 0.5; p = 0.007). Overall the maximum and mean lesional SUVs exhibited high correlations between PET/CT and PET/MR (ρ = 0.87 and ρ = 0.86, respectively; both p < 0.001). CONCLUSION: Despite a substantially later imaging time-point, the performance of simultaneous PET/MR was comparable to that of PET/CT in detecting lesions with increased [(11)C]choline uptake in patients with prostate cancer. Anatomical allocation of lesions was better with simultaneous PET/MR than with PET/CT, especially in the bone and pelvis. These promising findings suggest that [(11)C]choline PET/MR might have a diagnostic benefit compared to PET/CT in patients with prostate cancer, and now needs to be further evaluated in prospective trials.

FDG PET and PET/CT.

Molecular imaging with positron emission tomography (PET) using tumour-seeking radiopharmaceuticals has gained wide acceptance in oncology with many clinical applications. The hybrid imaging modality PET/CT allows assessing molecular as well as morphologic information at the same time. Therefore, PET/CT represents an efficient tool for whole body staging and re-staging within one imaging modality. In oncology the glucose analogue (18)F-fluorodeoxyglucose (FDG) is the most widely used PET and PET/CT radiopharmaceutical in clinical routine. FDG PET and PET/CT have been used for staging and re-staging tumour patients in numerous studies. This chapter will discuss the use and the main indications of FDG PET and PET/CT in oncology with special emphasis on lung cancer, oesophageal cancer, colorectal cancer, head and neck cancer, lymphoma and breast cancer (among other tumour entities). A review of the current literature will be given with respect to primary diagnosis, staging and diagnosis of recurrent disease (local, lymph node and distant metastases). Besides its integral role in diagnosis, staging and re-staging of disease in oncology, there is increasing evidence that FDG PET and PET/CT can significantly contribute to therapy response assessment possibly influencing therapeutic management and treatment planning, to therapy tumour control and prediction of prognosis in oncologic patients, which will also be discussed in this chapter.

PET-MRI fusion in head-and-neck oncology: current status and implications for hybrid PET/MRI.

PURPOSE: To review the current status and clinical effect of PET-MRI image fusion in the staging of head-and-neck cancer and to show its implications for imaging with future hybrid PET/MRI scanners. MATERIALS AND METHODS: We reviewed the current literature in order to provide an overview of the potential of the combination of the anatomic and functional imaging capabilities of magnetic resonance imaging (MRI) and of the potential for molecular and metabolic imaging with Positron emission tomography (PET). The research question was whether these image devices might be of synergistic value. RESULTS: PET with [18F]-fluorodeoxyglucose has shown promising results for the assessment of lymph node involvement in cancer, the identification of distant metastasis and synchronous and metachronous tumors, and the evaluation of tumor recurrence or carcinoma of an unknown primary. For morphologic imaging, MRI has several advantages compared with computed tomography in the head-and-neck area. This is mainly because of the superior soft tissue contrast and fewer artifacts from dental implants. Moreover, MRI allows functional imaging, such as the assessment of perfusion with dynamic contrast-enhanced MRI. The published data indicate that image fusion should be beneficial in the case of the recurrence of oromaxillofacial cancer and in the evaluation of potential metastatic lymph nodes. However, retrospective image fusion is technically demanding in the head-and-neck area, mainly because of the varied patient positions used for the various scanners and the anatomic complexity of this region. CONCLUSIONS: Combined PET/MRI scanners might overcome the above-named problems. Both sequential and fully integrated PET/MRI scanners are now available in selected departments, and future studies will show whether hybrid PET/MRI is of greater clinical value than PET/CT and retrospective image fusion techniques.

Radionuclide and hybrid imaging of recurrent prostate cancer.

Prostate cancer is one of the most common cancers in men, leading to substantial morbidity and mortality. After definitive therapy with surgery or radiation, many patients have biochemical relapse of disease--ie, an increase in their prostate-specific antigen level--which often precedes clinically apparent disease by months or even years. Therefore, imaging of the site and extent of tumour recurrence (local, regional, distant, or a combination) is of great interest. Conventional morphological imaging methods showed limited accuracy for assessment of recurrent prostate cancer; however, in recent years, functional and molecular imaging have offered the possibility of imaging molecular or cellular processes of individual tumours, often with more accuracy than morphological imaging. Hybrid imaging modalities (PET-CT, and single-photon emission CT [SPECT]-CT) have been introduced that combine functional and morphological data and allow whole-body imaging. Here, we review the contribution of radionuclide imaging and hybrid imaging for assessment of recurrent prostate cancer (local vs regional vs distant disease). We discuss available data on PET-CT and SPECT-CT, and provide an overview of experimental tracers and their preclinical and clinical development. Finally, we present a perspective on the potential of future hybrid magnetic resonance-PET imaging.

Value of a Dixon-based MR/PET attenuation correction sequence for the localization and evaluation of PET-positive lesions.

PURPOSE: In this study, the potential contribution of Dixon-based MR imaging with a rapid low-resolution breath-hold sequence, which is a technique used for MR-based attenuation correction (AC) for MR/positron emission tomography (PET), was evaluated for anatomical correlation of PET-positive lesions on a 3T clinical scanner compared to low-dose CT. This technique is also used in a recently installed fully integrated whole-body MR/PET system. METHODS: Thirty-five patients routinely scheduled for oncological staging underwent (18)F-fluorodeoxyglucose (FDG) PET/CT and a 2-point Dixon 3-D volumetric interpolated breath-hold examination (VIBE) T1-weighted MR sequence on the same day. Two PET data sets reconstructed using attenuation maps from low-dose CT (PET(AC_CT)) or simulated MR-based segmentation (PET(AC_MR)) were evaluated for focal PET-positive lesions. The certainty for the correlation with anatomical structures was judged in the low-dose CT and Dixon-based MRI on a 4-point scale (0-3). In addition, the standardized uptake values (SUVs) for PET(AC_CT) and PET(AC_MR) were compared. RESULTS: Statistically, no significant difference could be found concerning anatomical localization for all 81 PET-positive lesions in low-dose CT compared to Dixon-based MR (mean 2.51 ± 0.85 and 2.37 ± 0.87, respectively; p = 0.1909). CT tended to be superior for small lymph nodes, bone metastases and pulmonary nodules, while Dixon-based MR proved advantageous for soft tissue pathologies like head/neck tumours and liver metastases. For the PET(AC_CT)- and PET(AC_MR)-based SUVs (mean 6.36 ± 4.47 and 6.31 ± 4.52, respectively) a nearly complete concordance with a highly significant correlation was found (r = 0.9975, p < 0.0001). CONCLUSION: Dixon-based MR imaging for MR AC allows for anatomical allocation of PET-positive lesions similar to low-dose CT in conventional PET/CT. Thus, this approach appears to be useful for future MR/PET for body regions not fully covered by diagnostic MRI due to potential time constraints.

[11C]Choline as pharmacodynamic marker for therapy response assessment in a prostate cancer xenograft model.

PURPOSE: [(11)C]Choline has been established as a PET tracer for imaging prostate cancer. The aim of this study was to determine whether [(11)C]choline can be used for monitoring the effects of therapy in a prostate cancer mouse xenograft model. METHODS: The androgen-independent human prostate cancer cell line PC-3 was implanted subcutaneously into the flanks of 13 NMRI (nu/nu) mice. All mice were injected 4-6 weeks after xenograft implantation with 37 MBq [(11)C]choline via a tail vein. Dynamic imaging was performed for 60 min with a small-animal PET/CT scanner (Siemens Medical Solutions). Six mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. Seven mice were treated with PBS as a control. [(11)C]Choline imaging was performed prior to and 1, 2 and 3 weeks after treatment. To determine choline uptake the images were analysed in terms of tumour-to-muscle (T/M) ratios. Every week the size of the implanted tumour was determined with a sliding calliper. RESULTS: The PC-3 tumours could be visualized by [(11)C]choline PET. Before treatment the T/M(mean) ratio was 1.6+/-0.5 in the control group and 1.8+/-0.4 in the docetaxel-treated group (p=0.65). There was a reduction in the mean [(11)C]choline uptake after docetaxel treatment as early as 1 week after initiation of therapy (T/M ratio 1.8+/-0.4 before treatment, 0.9+/-0.3 after 1 week, 1.1+/-0.3 after 2 weeks and 0.8+/-0.2 after 3 weeks). There were no decrease in [(11)C]choline uptake in the control group following treatment (T/M ratio 1.6+/-0.5 before treatment, 1.7+/-0.4 after 1 week, 1.8+/-0.7 after 2 weeks and 1.7+/-0.4 after 3 weeks). For analysis of the dynamic data, a generalized estimation equation model revealed a significant decrease in the T/M(dyn) ratios 1 week after docetaxel treatment, and the ratio remained at that level through week 3 (mean change -0.93+/-0.24, p<0.001, after 1 week; -0.78+/-0.21, p<0.001, after 2 weeks; -1.08+/-0.26, p<0.001, after 3 weeks). In the control group there was no significant decrease in the T/M(dyn) ratios (mean change 0.085+/-0.39, p=0.83, after 1 week; 0.31+/-0.48, p=0.52, after 2 weeks; 0.11+/-0.30, p=0.72, after 3 weeks). Metabolic changes occurred 1 week after therapy and preceded morphological changes of tumour size during therapy. CONCLUSION: Our results demonstrate that [(11)C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a prostate cancer xenograft animal model. The results also indicate that PET with radioactively labelled choline derivatives might be a useful tool for monitoring responses to taxane-based chemotherapy in patients with advanced prostate cancer.

Tissue classification as a potential approach for attenuation correction in whole-body PET/MRI: evaluation with PET/CT data.

UNLABELLED: Attenuation correction (AC) of whole-body PET data in combined PET/MRI tomographs is expected to be a technical challenge. In this study, a potential solution based on a segmented attenuation map is proposed and evaluated in clinical PET/CT cases. METHODS: Segmentation of the attenuation map into 4 classes (background, lungs, fat, and soft tissue) was hypothesized to be sufficient for AC purposes. The segmentation was applied to CT-based attenuation maps from (18)F-FDG PET/CT oncologic examinations of 35 patients with 52 (18)F-FDG-avid lesions in the lungs (n = 15), bones (n = 21), and neck (n = 16). The standardized uptake values (SUVs) of the lesions were determined from PET images reconstructed with nonsegmented and segmented attenuation maps, and an experienced observer interpreted both PET images with no knowledge of the attenuation map status. The feasibility of the method was also evaluated with 2 patients who underwent both PET/CT and MRI. RESULTS: The use of a segmented attenuation map resulted in average SUV changes of 8% +/- 3% (mean +/- SD) for bone lesions, 4% +/- 2% for neck lesions, and 2% +/- 3% for lung lesions. The largest SUV change was 13.1%, for a lesion in the pelvic bone. There were no differences in the clinical interpretations made by the experienced observer with both types of attenuation maps. CONCLUSION: A segmented attenuation map with 4 classes derived from CT data had only a small effect on the SUVs of (18)F-FDG-avid lesions and did not change the interpretation for any patient. This approach appears to be practical and valid for MRI-based AC.