11C-choline Positron Emission Tomography Research Articles

Localization of Ectopic Hyperparathyroidism: Ultrasound Versus 99mTc-sestamibi, 4-Dimensional Computed Tomography, and 11C-choline Positron Emission Tomography/Computed Tomography

ObjectiveTo investigate the usefulness of ultrasound (US) for the localization of ectopic hyperparathyroidism and compare it with 99mTc-sestamibi (99mTc-MIBI), 4-dimensional computed tomography (4D-CT), and 11C-choline positron emission tomography/ computed tomography (PET/CT). MethodsOf the 527 patients with surgically confirmed primary hyperparathyroidism, 79 patients with ectopic hyperparathyroidism were enrolled. The diagnostic performance of US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT was calculated, and the factors affecting the sensitivity of US and 99mTc-MIBI were analyzed. ResultsEighty-three ectopic parathyroid lesions were found in 79 patients. The sensitivity was 75.9%, 81.7%, 95.1%, 83.3%, and 100% for US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT, respectively. The difference in sensitivity among these different modalities did not achieve statistical significance (P > .05). The US sensitivity was significantly higher for ectopic lesions in the neck region than for those in the anterior mediastinum/chest wall (85.9% vs. 42.1%, P < .001). The 99mTc-MIBI and 4D-CT sensitivity was not significantly different between these two groups (84.1% vs. 94.6%, P = .193 and 81.3% vs. 85.7%, P = 1). The 11C-choline PET/CT sensitivity was 100% in both groups. ConclusionsUS is a valuable tool for the localization of ectopic hyperparathyroidism, especially for ectopic lesions in the neck region.

Tumor-Derived Extracellular Vesicles Predict Clinical Outcomes in Oligometastatic Prostate Cancer and Suppress Antitumor Immunity

SABR has demonstrated clinical benefit in oligometastatic prostate cancer. However, the risk of developing new distant metastatic lesions remains high, and only a minority of patients experience durable progression-free response. Therefore, there is a critical need to identify which patients will benefit from SABR alone versus combination SABR and systemic agents. Herein we provide, to our knowledge, the first proof-of-concept of circulating prostate cancer-specific extracellular vesicles (PCEVs) as a noninvasive predictor of outcomes in oligometastatic castration-resistant prostate cancer (omCRPC) treated with SABR. We analyzed the levels and kinetics of PCEVs in the peripheral blood of 79 patients with omCRPC at baseline and days 1, 7, and 14 after SABR using nanoscale flow cytometry and compared with baseline values from cohorts with localized and widely metastatic prostate cancer. The association of omCRPC PCEV levels with oncological outcomes was determined with Cox regression models. Levels of PCEVs were highest in mCRPC followed by omCRPC and were lowest in localized prostate cancer. High PCEV levels at baseline predicted a shorter median time to distant recurrence (3.5 vs 6.6 months; P=.0087). After SABR, PCEV levels peaked on day 7, and median overall survival was significantly longer in patients with elevated PCEV levels (32.7 vs 27.6 months; P=.003). This suggests that pretreatment PCEV levels reflect tumor burden, whereas early changes in PCEV levels after treatment predict response to SABR. In contrast, radiomic features of 11C-choline positron emission tomography and computed tomography before and after SABR were not predictive of clinical outcomes. Interestingly, PCEV levels and peripheral tumor-reactive CD8 T cells (TTR; CD8+ CD11ahigh) were correlated. This original study demonstrates that circulating PCEVs can serve as prognostic and predictive markers to SABR to identify patients with "true" omCRPC. In addition, it provides novel insights into the global crosstalk, mediated by PCEVs, between tumors and immune cells that leads to systemic suppression of immunity against CRPC. This work lays the foundation for future studies to investigate the underpinnings of metastatic progression and provide new therapeutic targets (eg, PCEVs) to improve SABR efficacy and clinical outcomes in treatment-resistant CRPC.

Utility of radiomic zones for risk classification and clinical outcome predictions using supervised machine learning during simultaneous 11 C-choline PET/MRI acquisition in prostate cancer patients.

In most radiomic studies related to cancer research, the traditional tumor-centric view has predominated. In this retrospective study, we go beyond the single-tumor region and investigate the utility of proposed radiomic zones for risk classification and clinical outcome predictions using radiomic features extracted from 11 C-choline positron emission tomography (PET) imaging and supervised machine learning in prostate tumors. Seventy-seven prostate tumors were selected and delineated. The prostate organ was divided into three radiomic zones, with zone-1 being the metabolic tumor zone, zone-2 the proximal peripheral tumor zone, and zone-3 the extended peripheral tumor zone. LIFEx was used for PET-radiomic feature extraction. Risk groups were created using Gleason scores (GS), prostate-specific antigen (PSA) levels, clinical TNM staging, and progression-free survival (PFS). Random forest (RF) and AdaBoost advanced machine learning algorithms were used for supervised machine learning. Accuracy, positive predictive value, area under the receiver operating characteristic curve (AreaROC), and other metrics were calculated for comparisons of predictive performance between zones. For the GS risk classification group, the accuracies of risk classification predictions were 71%, 71%, and 67% using RF and 65%, 64%, and 63% using AdaBoost for zones -1, -2, and -3, respectively. For the PSA group, the accuracies of risk classification predictions were 74%, 65%, and 64% using RF and 76%, 66%, and 67% using AdaBoost for zones -1, -2, and -3, respectively. For the TNM group, the accuracies of risk classification predictions were 68%, 76%, and 78% using RF and 66%, 75%, and 80% using AdaBoost for zones -1, -2, and -3, respectively. For the PFS group, the accuracies of clinical outcome predictions were 77%, 75%, and 83% using RF and 77%, 74%, and 83% using AdaBoost in zones -1, -2, and -3, respectively. We proposed three radiomic zones with different standard uptake value characteristics and created four risk groups of prostate cancer patients for testing this idea. We showed that these radiomic zones have different predicting strengths in classifying risk groups and might allow us to identify a radiomic zone with higher accuracy for patient outcome prediction.

Value of 11C-Choline PET/CT-Based Multi-Metabolic Parameter Combination in Distinguishing Early-Stage Prostate Cancer From Benign Prostate Diseases.

PurposeThe most common disadvantage of 11C-choline positron emission tomography and computed tomography (PET/CT) in diagnosing early-stage prostate cancer (PCa) is its poor sensitivity. In spite of many efforts, this imaging modality lacks the ideal parameter of choline metabolism for the diagnosis of PCa, and the single metabolic parameter, that is, maximal standardized uptake value (SUVmax), based on this imaging modality is insufficient. 11C-choline PET/CT-based multi-metabolic parameter combination can help break this limitation.Materials and MethodsBefore surgery, SUVmax of choline, which is the most common metabolic parameter of 11C-choline PET/CT, mean standardized uptake value (SUVmean), prostate-to-muscle (P/M) ratio, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from 74 patients with histologically proven PCa were quantified. A total of 13 patients with focal chronic prostatitis without severe features and 30 patients with benign prostate hyperplasia were used for comparison. Univariable and multivariable analyses were performed to compare the patient characteristics and metabolic parameters of 11C-choline PET/CT. The performance of single parameters and the combination of parameters were assessed by using logistic regression models.ResultsThe comparable c-statistics, which mean the area under the ROC curve in the logistic regression model, of SUVmax, SUVmean, and P/M ratio are 0.657, 0.667, and 0.672, respectively. The c-statistic significantly rose to 0.793 when SUVmax and SUVmean were combined with the P/M ratio. This parameter combination performed the best for PCa cases with all biochemical recurrence risks and for PCa patients grouped by different risk. The greatest improvement over a single parameter, such as P/M ratio, was noted in the group of low-risk PCa, with values of 0.535 to 0.772 for the three-parameter combination. And in the histopathological level, the Ki-67 index is positively correlated with the P/M ratio (r=0.491, p=0.002).ConclusionP/M ratio is a more ideal parameter than SUVmax as a single parameter in early-stage PCa diagnosis. According to our data, the combination of SUVmax, SUVmean, and P/M ratio as a composite parameter for diagnosis of early stage PCa improves the diagnostic accuracy of 11C-choline PET/CT.

Diffusion-weighted MRI, 11C-choline PET/CT, and 18F-FDG PET/CT for predicting the Gleason score in prostate cancer.

To evaluate diffusion-weighted magnetic resonance imaging (DWI), 11C-choline positron emission tomography (PET), and fluorine-18-fluorodeoxyglucose (18F-FDG) PET for predicting Gleason score in prostate cancer patients. The study cohort included 11 patients with biopsy-proven prostate cancer who underwent DWI, 11C-choline PET, and 18F-FDG PET examinations before treatment. The correlations of Gleason score with those findings were determined using Spearman's test. Multi-technique imaging performance for separating higher Gleason score (≥8) cases was also examined. Both diffusion coefficient (ADC) map and 11C-choline PET/computed tomography (CT) findings showed prostate cancer in all 11 patients, while 18F-FDG PET/CT was only successful in 6 (54.5%) cases, thus no further evaluations of that modality were performed. A moderately negative correlation was observed between Gleason score and ADC value for the primary tumor shown by DWI, though the difference was not significant (r=-0.49, P=0.13). In contrast, a strongly significant positive correlation was observed between Gleason score and maximum standardized uptake value (SUVmax) for the primary tumor in 11C-choline PET findings (r=0.85, P=0.0010). Sensitivity, specificity, and accuracy for separating higher (≥8) from lower (≤7) Gleason score were 87.5%, 33.3%, and 72.7%, respectively, with a best cut-off value of 0.78 for ADC map, and 87.5%, 100%, and 90.9%, respectively, with a best cut-off value of 6.0 for 11C-choline PET. Carbon-11-choline PET was found have a greater correlation with Gleason score than DWI and is considered to be more useful to predict a higher score in patients with prostate cancer. Fluorine-18-FDG PET was limited because of low sensitivity.

Retrospective review of 11C-choline detected thoracic lesions in prostate cancer.

325 Background: Prostate cancer recurrence is detected by serum measurements of prostate specific antigen (PSA). Upon PSA elevation, locating sites of recurrence is important to guiding treatment and affecting patient outcomes. The imaging modalities in current practice have varying sensitivities and specificities and often miss early recurrent disease. 11C-choline positron emission tomography (11C-PET) may be able to detect occult disease and guide treatment decisions earlier in the clinical course. We assessed a case series of patients who underwent 11C-PET imaging and were identified to have thoracic disease to estimate the benefit of detection with this modality. Methods: Clinical records were retrospectively reviewed of seventy patients from thoracic oncology teams at Mayo Clinic in Rochester, Minnesota. Patients who had thoracic +/- extra-thoracic metastases on 11C-PET imaging were followed, noting changes in treatment and PSA trends to look for biochemical recurrence of disease. Results: Seventy patients with thoracic metastases discovered on 11C-PET imaging were initially identified. Median time to choline-avid disease from original diagnosis was 82 (IQR: 40-129) months with a median PSA at time of choline of 7.4 (IQR: 3.1-15.7). 11C-PET findings showed 28 patients with metastases limited to the thorax and 42 patients with thoracic and extra-thoracic metastases. After 11C-PET imaging, 1 patient underwent localized therapy only (radiation and surgery), 44 patients underwent systemic therapy only (chemotherapy or hormonal therapy), 19 patients underwent both localized (cryotherapy, radiation, or surgery) and systemic therapy, 3 patients underwent no further treatment, and 3 patients were lost to follow up. After a median follow-up of 36.5 (IQR: 13-52) months, 30 patients had no recurrence and 20 had evidence of biochemical recurrence. For those who underwent local therapy (N=21), 11 had no recurrence of disease. Conclusions: Choline-based imaging may earlier identify metastatic disease that is amenable to local therapy. Further studies are needed to validate the effectiveness of 11C-PET in identifying early, responsive metastatic prostate cancer and its utility in affecting patient outcomes.

Reirradiation of Locally Recurrent Prostate Cancer With Volumetric Modulated Arc Therapy

This study explores the efficacy and safety of reirradiation with modern radiation therapy techniques in patients previously irradiated for prostate cancer and affected by local relapse of disease. Patients affected by previously irradiated prostate cancer were enrolled in this reirradiation study if they had a biochemical relapse and a 11C-choline positron emission tomography scan revealing the presence of a local recurrence of disease. Reirradiation consisted of a stereotactic treatment delivered by image guided radiation therapy-volumetric modulated arc therapy with flattening filter-free technology in 5 daily fractions. Twenty-three patients underwent reirradiation to the prostate, prostatic bed, or prostate and local recurrence. Re-treatment consisted of a median total dose of 25Gy in 5 fractions. A biochemical response was observed in all cases. Acute toxicity was mainly genitourinary (GU) grade 1 to 2 (n=13; 56.5%). One patient (4.3%) had grade 3 hematuria. A grade 1 GU late toxicity was registered in 4 patients (17.4%) and grade 3 in 1 patient (4.3%, urethral obstruction). Gastrointestinal toxicity was negligible. Regression analysis showed that only a short elapsed time in months from primary radiation therapy was significantly correlated with acute GU toxicity. After a median follow-up of 33months (range, 5-58months), the median biochemical recurrence-free survival was 19months, and the 2-year biochemical recurrence-free survival (BRFS) was 41.7%. Median local control was 30months; the 2-year local control rate was 58.1%. Reirradiation of patients with prostate cancer who underwent previous radiation therapy is a valuable option that can be safely considered to delay the beginning of hormonal treatment.

Accuracy of 11C-choline positron emission tomography in differentiating glioma recurrence from radiation necrosis: A systematic review and meta-analysis.

Distinguishing glioma recurrence from the necrosis after radiation therapy and/or chemotherapy is a crucial clinical issue, for the different diagnosis will lead to divergent treatments. The accurate judgment is barely achieved by conventional imaging methods. We therefore assume it is of need to exert a meta-analysis to evaluate the diagnostic accuracy of 11C-choline positron emission tomography (PET), to achieve this goal. We searched the PubMed, Embase, and Chinese Biomedical databases comprehensively to select eligible studies and assessed the quality of each article included (up to May 31, 2018). Fixed-effects models were used. Summary diagnostic accuracy of 11C-choline PET was obtained from pooled analysis. Five articles comprising 6 studies with total 118 patients (134 scans) were enrolled for the meta-analysis. There was no heterogeneity or publication bias among the included studies. The pooled sensitivity and specificity were 0.87 (95% confidence interval [CI]: 0.78, 0.93) and 0.820 (95% CI: 0.69, 0.91), respectively. The pooled diagnostic odds ratio was 35.50 (95% CI: 11.70, 107.75). The area under the curve was 0.9170 (95% CI: 0.8504, 0.9836), with Q* index equaling to 0.8499. The diagnostic accuracy of each subgroup showed no statistical differences with that of the overall group. This meta-analysis indicated 11C-choline has high diagnostic accuracy for the identification of tumor relapse from radiation induced necrosis in gliomas.

Preoperative Staging With 11C-Choline PET/CT Is Adequately Accurate in Patients With Very High-Risk Prostate Cancer.

To evaluate the accuracy of 11C-choline positron emission tomography (PET)/computed tomography (CT) for nodal staging of prostate cancer (PCa) in different populations of high-risk patients. We evaluated 262 individuals with intermediate- or high-risk PCa submitted to radical prostatectomy and extended pelvic lymph node dissection. Within men with high-risk disease, we identified a subgroup of individuals harboring very high-risk (VHR, n= 28) disease: clinical stage≥ T2c and more than 5 cores with Gleason score 8-10; primary biopsy Gleason score of 5; 3 high-risk features; or prostate-specific antigen≥ 30 ng/mL. The diagnostic accuracy of PET/CT and contrast-enhanced CT (CECT) was assessed after stratifying patients according to risk group classification on a patient- and anatomic region-based analysis. On patient-based analysis, considering high-risk patients (n=155), 11C-choline PET/CT versus CECT had sensitivity and specificity of 50% and 76% versus 21% and 92%, respectively. Considering VHR men as separate subgroups (n= 28), 11C-choline PET/CT versus CECT had sensitivity and specificity of 71% and 93% versus 25% and 79%, respectively. Accordingly, in the VHR category, the area under the curve of 11C-choline PET/CT versus CECT was 0.86 (95% confidence interval, 0.71-1.0) versus 0.69 (95% confidence interval, 0.52-0.86), respectively. On anatomic region-based analysis, considering the VHR group, 11C-choline PET/CT versus CECT had sensitivity and specificity of 70.6% and 95.5% versus 35.3% and 98.5%, respectively. Patients with VHR characteristics could represent the ideal candidate to undergo disease staging with PET/CT before surgery with the highest cost efficacy.

Identification of Recurrence Sites Following Post-Prostatectomy Treatment for Prostate Cancer Using 11C-Choline Positron Emission Tomography and Multiparametric Pelvic Magnetic Resonance Imaging

We describe anatomical sites of recurrence in patients with prostate cancer who had biochemical recurrence following radical prostatectomy and who received radiotherapy and/or androgen deprivation therapy postoperatively. We performed 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging. After radiotherapy and/or androgen deprivation therapy patients who underwent radical prostatectomy were evaluated by 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging to determine recurrence patterns and clinicopathological features. Recurrent sites were described as local only (seminal vesicle bed/prostate fossa, vesicourethral anastomosis and bladder neck) or distant metastatic disease. Features associated with the identification of any distant metastatic disease were evaluated by multivariable logistic regression. A total of 550 patients were identified. Treatment included androgen deprivation therapy in 108, radiotherapy in 201, and androgen deprivation therapy and radiotherapy in 241. Median prostate specific antigen at evaluation was 3.9, 3.6 and 2.8 ng/ml in patients treated with androgen deprivation therapy, radiotherapy and a combination, respectively. Recurrence developed locally in 77 patients (14%), as distant metastasis only in 411 (75%), and as local and distant metastatic disease in 62 (11%). On multivariable analysis treatment with radiotherapy (OR 7.18, 95% CI 2.92-17.65), and radiotherapy and hormonal therapy (OR 9.23, 95% CI 3.90-21.87, all p <0.01) was associated with increased odds of distant failure at evaluation. The combination of 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging successfully identified patterns of recurrence after postoperative radiotherapy and/or androgen deprivation therapy at a median prostate specific antigen of less than 4 ng/ml. Half of this cohort had local only recurrence and/or a low disease burden limited to pelvic lymph nodes. These patients may benefit from additional local therapy. These data and this analysis may facilitate the evaluation of such patients with biochemically recurrent prostate cancer.

11C-choline PET/CT and whole-body MRI including diffusion-weighted imaging for patients with recurrent prostate cancer.

PurposeTo compare the detection efficacy of 11C-choline positron emission tomography and computed tomography (PET/CT) with whole-body magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) in patients with suspected recurrent prostate cancer.Materials and MethodsFifty-seven patients (mean age 68, range 54-80 years) underwent 11C-choline PET/CT and MRI using T1-weighted (T1w), short-tau inversion recovery (STIR), and DWI. Two readers visually rated suspicious lesions on a 5-point scale in 20 different regions. Clinical follow-up and histopathology served as the standard of reference (SOR).ResultsFifty patients (mean PSA 29.9, range 1.0-670 ng/mL) had at least one positive lesion according to the SOR. Twenty-four patients had local recurrence (LR), 27 had lymph node (LN) involvement, and 22 had bone metastases. The overall detection rates for PET/CT and MRI on a patient basis were 94% and 88%, respectively (p = 0.07). The PSA level (>2 ng/mL vs ≤2 ng/mL) significantly influenced the overall performance of PET/CT (p = 0.003) and MRI (p = 0.03). PET/CT was significantly superior to MRI in detecting LR (p = 0.03) and bone metastasis (p = 0.02). We found no difference with respect to the detection of LN metastasis (p = 0.65).Conclusion11C-choline PET/CT was superior in the detection of local recurrence and bone metastasis on a regional basis. Whole-body MRI including DWI showed similar diagnostic accuracy only for detecting lymph node metastases. Compared with 11C-choline PET/CT, therefore, whole-body MRI including DWI cannot serve as alternative imaging modality for restaging prostate cancer.

Contemporary Mapping of Post-Prostatectomy Prostate Cancer Relapse with 11C-Choline Positron Emission Tomography and Multiparametric Magnetic Resonance Imaging

We identify sites and patterns of cancer recurrence in patients with post-prostatectomy biochemical relapse using 11C-choline positron emission tomography/computerized tomography and endorectal coil multiparametric magnetic resonance imaging. Between January 2008 and June 2015, 2,466 men underwent choline positron emission tomography for suspected prostate cancer relapse at our institution. Of these men 202 did not receive hormone or radiation therapy, underwent imaging with choline positron emission tomography and multiparametric magnetic resonance imaging, and were found to have disease recurrence. Overall patterns of recurrence were described, and factors associated with local only recurrence were evaluated using univariable and multivariable logistic regression. Median prostate specific antigen at positive scan was 2.3 ng/ml (IQR 1.4-5.5) with a median time from prostate specific antigen relapse to lesion visualization of 15 months (IQR 4.8-34.2). Of these 202 men 68 (33%) exhibited local only, 45 (22%) local plus metastatic and 89 (45%) metastatic only relapse. Pelvic node only relapse was observed in 39 (19%) men. Median prostate specific antigen at positive imaging for patients with local only, metastatic only and local plus metastatic relapse was 2.3, 2.7 and 2.2 ng/ml (p=0.46), with a median interval from biochemical recurrence to positive scan of 33.5, 7.0 and 15.0 months, respectively (p <0.001). On multivariable analysis time from biochemical recurrence to positive imaging was independently associated with local only recurrence (OR 1.10 for every 6-month increase, p=0.012). Combined choline positron emission tomography and multiparametric magnetic resonance imaging evaluation of biochemical recurrence after prostatectomy reveals an anatomically diverse pattern of recurrence. These findings have implications for optimizing the salvage treatment of patients with prostate cancer with relapse following surgery.

11C-Choline PET guided resection of thoracic metastases from prostatic adenocarcinoma.

e16528Background: 11C-choline positron emission tomography (11C-PET) is an FDA approved test for the identification of recurrent and metastatic prostate cancer in patients with biochemical recurren...

Role for (11)C-choline PET in active surveillance of prostate cancer.

Active surveillance (AS) is an increasingly popular management strategy for men diagnosed with low-risk indolent prostate cancer. Current tests (prostate-specific antigen [PSA], clinical staging, and prostate biopsies) to monitor indolent disease lack accuracy. (11)C-choline positron emission tomography (PET) has excellent detection rates in local and distant recurrence of prostate cancer. We examine (11)C-choline PET for identifying aggressive prostate cancer warranting treatment in the AS setting. In total, 24 patients on AS had clinical assessment and PSA testing every 6 months and (11)C-choline PET and prostate biopsies annually. The sensitivity and specificity to identify prostate cancer and progressive disease (PD) were calculated for each (11)C-choline PET scan. In total, 62 biopsy-paired, serial (11)C-choline PET scans were analyzed using a series of standard uptake value-maximum (SUVmax) cut-off thresholds. During follow-up (mean 25.3 months), 11 of the 24 low-risk prostate cancer patients developed PD and received definitive treatment. The prostate cancer detection rate with (11)C-choline PET had moderate sensitivity (72.1%), but low specificity (45.0%). PD prediction from baseline (11)C-choline PET had satisfactory sensitivity (81.8%), but low specificity (38.5%). The addition of clinical parameters to the baseline (11)C-choline PET improved specificity (69.2%), with a slight reduction in sensitivity (72.7%) for PD prediction. Addition of (11)C-choline PET imaging during AS may help to identify aggressive disease earlier than traditional methods. However, (11)C-choline PET alone has low specificity due to overlap of SUV values with benign pathologies. Triaging low-risk prostate cancer patients into AS versus therapy will require further optimization of PET protocols or consideration of alternative strategies (i.e., magnetic resonance imaging, biomarkers).

Final analysis of a prospective trial on functional imaging for nodal staging in patients with prostate cancer at high risk for lymph node involvement

PurposeAccurate staging modalities to diagnose lymph node involvement in patients with prostate cancer (PCa) are lacking. We wanted to prospectively assess sensitivity, specificity, and positive predictive value (PPV) and negative predictive value of 11C-choline positron emission tomography (PET)-computed tomography (CT) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for nodal staging in patients with PCa at high risk for lymph node involvement. Material and methodsIn total, 75 patients with a risk≥10% but<35% for lymph node (LN) metastases (Partin tables) who had N0 lesions based on the findings of contrast-enhanced CT scans were included. Patients underwent 11C-choline PET-CT and DW MRI before surgery, which consisted of a superextended lymph node dissection followed by radical prostatectomy. LNs were serially sectioned and histopathologically examined after pankeratin staining. These results were used as the gold standard to compare with the imaging results. ResultsOf 1,665 resected LNs (median = 21, range: 7–49), 106 affected LNs (median = 2, range: 1–10) were found in 37 of 75 patients (49%). On a region-based analysis, we found a low sensitivity of 8.2% and 9.5% and a PPV of 50.0% and 40.0% for 11C-choline PET-CT and DW MRI, respectively. The patient-based analysis showed a sensitivity of 18.9% and 36.1% for and a PPV of 63.6% and 86.7% 11C-choline PET-CT and DW MRI, respectively. Even when both imaging modalities were combined, sensitivity values remained too low to be clinically useful. ConclusionsBecause of the low sensitivity, there is no indication for routine clinical use of either 11C-choline PET-CT or DW MRI for LN staging in patients with PCa, in whom CT scan findings were normal.

Use of ¹¹C-Choline positron emission tomography/computed tomography to investigate the mechanism of choline metabolism in lung cancer.

The present study was conducted to investigate the 11C-Choline metabolic mechanism and examine the association between 11C-Choline metabolism and uptake in different pathological types of lung cancer. A total of 18 tumor specimens and corresponding normal lung tissues were collected from patients who were diagnosed with lung cancer using 11C-Choline positron emission tomography (PET)/computed tomography (CT) imaging between January 2007 and December 2008 at the Medical Imaging Center of the Provincial Hospital Affiliated to Shandong University. The diagnosis was further confirmed pathologically following surgery. Reverse transcription polymerase chain reaction and western blotting were used to investigate the expression of choline acetyltransferase (ChAT) and choline kinase α (ChoK) in lung cancer tissue and normal lung tissue. The 11C-Choline PET/CT data were analyzed visually and semiquantitatively. Compared with the expression in the normal lung tissues, the mRNA and protein expression of ChAT and ChoK increased in nine and 14 of the 18 lung tumors, respectively. A total of eight of the 18 tumors exhibited significantly increased expression, while three exhibited no expression of ChoK and ChAT. All lung cancer lesions were visualized with 11C-Choline PET/CT imaging. The phosphorylation and acetylation pathways of choline metabolism may be important in 11C-Choline uptake and metabolism in different pathological types of lung cancer.

Bevacizumab treatment leads to observable morphological and metabolic changes in brain radiation necrosis.

We investigated morphological and metabolic changes of radiation necrosis (RN) of the brain following bevacizumab (BEV) treatment by using neuroimaging. Nine patients with symptomatic RN, who had already been treated with radiation therapy for malignant brain tumors (6 glioblastomas, 1 anaplastic oligodendroglioma, and 2 metastatic brain tumors), were enrolled in this prospective clinical study. RN diagnosis was neuroradiologically determined with Gd-enhanced MRI and 11C-methionine positron emission tomography (MET-PET). RN clinical and radiological changes in MRI, magnetic resonance spectroscopy (MRS) and PET were assessed following BEV therapy. Karnofsky performance status scores improved in seven patients (77.8 %). Both volumes of the Gd-enhanced area and FLAIR-high area from MRI decreased in all patients after BEV therapy and the mean size reduction rates of the lesions were 80.0 and 65.0 %, respectively. MRS, which was performed in three patients, showed a significant reduction in Cho/Cr ratio after BEV therapy. Lesion/normal tissue (L/N) ratios in MET- and 11C-choline positron emission tomography (CHO-PET) decreased in 8 (89 %) and 9 patients (100 %), respectively, and the mean L/N ratio reduction rates were 24.4 and 60.7 %, respectively. BEV-related adverse effects of grade 1 or 2 (anemia, neutropenia and lymphocytopenia) occurred in three patients. These results demonstrated that BEV therapy improved RN both clinically and radiologically. BEV therapeutic mechanisms on RN have been suggested to be related not only to the effect on vascular permeability reduction by repairing the blood-brain barrier, but also to the effect on suppression of tissue biological activity, such as immunoreactions and inflammation.

Diffusion-weighted MRI, 11C-choline PET and 18F-fluorodeoxyglucose PET for predicting the Gleason score in prostate carcinoma

To evaluate the accuracy of transrectal ultrasound-guided (TRUS) biopsy, diffusion-weighted (DW) magnetic resonance imaging (MRI), (11)C-choline (CHOL) positron emission tomography (PET), and (18)F-fluorodeoxyglucose (FDG) PET in predicting the prostatectomy Gleason risk (GR). The study included 21 patients who underwent TRUS biopsy and multi-technique imaging before radical prostatectomy. Values from five different tests (TRUS biopsy, DW MRI, CHOL PET, FDG PET, and combined DW MRI/CHOL PET) were correlated with the prostatectomy GR using Spearman's ρ. Tests that were found to have significant correlations were used to classify patients into GR groups. The following tests had significant correlations with prostatectomy GR: TRUS biopsy (ρ = 0.617, P = 0.003), DW MRI (ρ = -0.601, P = 0.004), and combined DW MRI/CHOL PET (ρ = -0.623, P = 0.003). CHOL PET alone and FDG PET only had weak correlations. The correct GR classification rates were 67% with TRUS biopsy, 67% with DW MRI, and 76% with combined DW MRI/CHOL PET. DW MRI and combined DW MRI/CHOL PET have significant correlations and high rates of correct classification of the prostatectomy GR, the strength and accuracy of which are comparable with TRUS biopsy. • Accurate determination of the Gleason score is essential for prostate cancer management. • DW MRI ± CHOL PET correlated significantly with prostatectomy Gleason score. • These correlations are similar to that between TRUS biopsy and prostatectomy.

Does 11C-choline PET-CT contribute to multiparametric MRI for prostate cancer localisation?

The aim of this work was to determine whether 11C-choline positron emission tomography (PET)-computed tomography (CT) makes a positive contribution to multiparametric magnetic resonance imaging (MRI) for localisation of intraprostatic tumour nodules. A total of 73 patients with biopsy-proven intermediate- and high-risk prostate cancer were enrolled in a prospective imaging study consisting of T2-weighted (T2w), dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI and 11C-choline PET-CT before radical prostatectomy. Cancerous regions were delineated on the whole-mount prostatectomy sections and on the different MRI modalities and analysed in 24 segments per patient (3 sections, 8 segments each). To analyse PET-CT images, standardized uptake values (SUV) were calculated per segment. In total, 1,752 segments were analyzed of which 708 (40.4%) were found to be malignant. A high specificity (94.7, 93.6 and 92.2%) but relatively low sensitivity (31.2, 24.9 and 44.1%) for tumour localisation was obtained with T2w, DCE and DW MRI, respectively. Sensitivity values significantly increased when combining all MRI modalities (57.2%). For PET-CT, mean SUVmax of malignant octants was significantly higher than mean SUVmax of benign octants (3.68±1.30 vs. 3.12±1.02, p<0.0001). In terms of accuracy, the benefit of adding PET-CT to (multiparametric) MRI was less than 1%. The additional value of 11C-choline PET-CT to MRI in localising intraprostatic tumour nodules is limited, especially when multiparametric MRI is used.

Multimodal Elucidation of Choline Metabolism in a Murine Glioma Model Using Magnetic Resonance Spectroscopy and 11C-Choline Positron Emission Tomography

The metabolites, transporters, and enzymes involved in choline metabolism are regarded as biomarkers for disease progression in a variety of cancers, but their in vivo detection is not ideal. Both magnetic resonance spectroscopy [MRS using chemical shift imaging (CSI) total choline (tCho)] and C-choline positron emission tomography (PET) can probe this pathway, but they have not been compared side by side. In this study, we used the spontaneous murine astrocytoma model SMA560 injected intracranially into syngeneic VM/Dk mice, analyzing animals at various postimplantation time points using dynamic microPET imaging and CSI MRS. We observed an increase in tumor volume and C-choline uptake between days 5 and 18. Similarly, tCho levels decreased at days 5 to 18. We found a negative correlation between the tCho and PET results in the tumor and a positive correlation between the tCho tumor-to-brain ratio and choline uptake in the tumor. PCR results confirmed expected increases in expression levels for most of the transporters and enzymes. Using MRS quantification, a good agreement was found between CSI and C-choline PET data, whereas a negative correlation occurred when CSI was not referenced. Thus, C-choline PET and MRS methods seemed to be complementary in strengths. While advancing tumor proliferation caused an increasing C-choline uptake, gliosis and inflammation potentially accounted for a high peritumoral tCho signal in CSI, as supported by histology and secondary ion mass spectrometry imaging. Our findings provide definitive evidence of the use of MRS, CSI, and PET for imaging tumors in vivo.