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Analizar el rendimiento diagnóstico de la PET/TC con 11C-colina en el seguimiento del cáncer de próstata (CaP), especialmente en pacientes con antígeno prostático específico (PSA) > 1 ng/ml. Se evaluaron retrospectivamente 329 exploraciones PET/TC con 11C-colina de 191 pacientes (68,2 ± 7,2 años) con CaP con recaída bioquímica o en seguimiento (PSA en el momento de la PET/TC: 13,0 ± 84,2 ng/ml). El tratamiento inicial fue prostatectomía radical en 81 pacientes y otros tratamientos (radioterapia, quimioterapia, hormonoterapia) en 110. La PET/TC se adquirió 20 min después de la inyección de 555-740 MBq de 11C-colina. El seguimiento mínimo fue superior a 12 meses. Doscientas diecinueve (66,6%) de las 329 exploraciones PET/TC fueron positivas. El porcentaje de positivos fue significativamente mayor en los pacientes con otro tratamiento inicial diferente a la prostatectomía radical (85,6 frente a 43,6%, respectivamente). Ciento treinta PET/TC (59,4%) mostraron recidiva local, 48 (21,9%) a distancia y 41 (18,7%) local más a distancia. El abordaje terapéutico inicial se modificó en 139 casos (63,5%). De las 81 PET/TC con 11C-colina realizadas con PSA < 1 ng/ml, 23 (28,4%) fueron positivas. El abordaje terapéutico inicial se modificó en 9 (11,1%). Tres de 63 pacientes (4,8%) fallecieron por CaP. La PET/TC con 11C-colina demostró su eficacia en el seguimiento y la reestadificación del CaP, incluso en pacientes con PSA sérico < 1 ng/ml. El rendimiento diagnóstico fue diferente según el tratamiento inicial al que fueron sometidos los pacientes, siendo mayor en aquellos tratados inicialmente con otros tratamientos distintos de la PR prostatectomía radical. Our aim was to analyse the performance of 11C-choline PET/CT in prostate cancer (PCa) surveillance, especially in patients with prostate specific antigen (PSA) < 1 ng/ml. Three hundred and twenty-nine 11C-choline PET/CT examinations from 191 patients (68.2 ± 7.2 years) submitted for PCa surveillance or biochemical recurrence were retrospectively evaluated (PSA at study was 13.0 ± 84.2 ng/ml). Main initial treatment was radical prostatectomy in 81 patients, and other treatments (radiotherapy, chemotherapy, hormonotherapy) in 110. PET/CT was acquired 20 min after injection of 555-740 MBq of 11C-choline. Minimum follow-up was 12 months. Two hundred and nineteen (66.6%) out of the 329 PET/CT examinations were positive. The percentage of positive examinations was significantly higher in patients with other initial treatment than radical prostatectomy compared to patients with radical prostatectomy (85.6 vs. 43.6%, respectively). One hundred and thirty PET/CT (59.4%) showed local recurrence, 48 (21.9%) distant recurrence, and 41 (18.7%) local plus distant recurrence. Initial therapeutic approach was changed in 139 cases (63.5%). In the subgroup of 81 11C-choline PET/CT scans performed with PSA < 1 ng/ml, 23 (28.4%) showed a positive result. Initial therapeutic approach was changed in 9 (11.1%). Three (4.8%) out of 63 patients died as per PCa. 11C-choline PET/CT demonstrated its effectiveness in PCa surveillance and restaging, even in patients with serum PSA < 1 ng/ml. The diagnostic performance was different depending on the initial treatment, been higher in patients with non-surgical treatment. [ABSTRACT FROM AUTHOR]

Background: Positron emission tomography/computed tomography (PET/CT) has been used as a noninvasive imaging method to assess the disease extent in patients. Objective: To assess the effective radiation dose in patients who underwent PET/CT. Materials and Methods: The present study included 24 patients with cholangiocarcinoma (CCA) or hepatocellular carcinoma (HCC), aged 39 to 74 years, who underwent 11C-choline and 18F-FDG whole body PET/CT scans at National Cyclotron and PET Centre, Chulabhorn Hospital. The radiation absorbed doses to target organs and effective whole body doses were calculated from ICRP 106 publication for 18F-FDG and the US FDA publication for 11C-choline. Results: The average whole body effective dose from the 18F-FDG PET scan was 6.81±1.09 mSv and from the CT scan was 12.95±3.33 mSv. For 11C-choline, the effective whole-body dose was 1.90±0.40 mSv from the PET scan and 14.20±3.14 mSv from the CT scan. Our results showed that 11C-choline accumulates mainly in the liver, lungs and stomach, while the accumulation of 18F-FDG is mainly in bladder, lungs and liver. Conclusion: The results showed that the effective dose from CT modality between 18F-FDG and 11C-choline patients were not significantly different. However, the average effective dose for patients undergoing whole body 18F-FDG PET was 3.6 times higher than with 11C-choline PET. [ABSTRACT FROM AUTHOR]

PurposeStudies have indicated that PSMA-positive ganglia represent a diagnostic pitfall for nuclear medicine physicians. No studies have described choline and FDG uptake in ganglia, which may be a source of misdiagnosis. Herein, we described the percentage and uptake pattern of 68Ga-PSMA, 11C-choline and 18F-FDG PET/CT in ganglia and evaluated the heterogeneous metabolic patterns of ganglia to differentiate from lymph node metastases (LNM).MethodsThirty-nine patients who underwent 11C-choline PET/CT and 120 patients who underwent 68Ga-PSMA PET/CT and 18F-FDG PET/CT were retrospectively analyzed. The prevalence of PSMA-positive, choline-positive and FDG-positive ganglia was determined, the SUVmax of ganglia in different locations were measured, and the configuration was described. The SUVmax cutoff of PSMA-PET, choline-PET and FDG-PET was determined by ROC curve analysis to differentiate ganglia from LNM.Results329 PSMA-positive ganglia were identified in 120 patients, 95 choline-positive ganglia were identified in 39 patients, and 39 FDG-positive ganglia were identified in 34 patients. PSMA-positive uptake was observed in 98.3%, 95.8%, and 80.0% of cervical, coeliac, and sacral ganglia, respectively. Choline-positive uptake was observed in 84.6%, 97.4%, and 61.5% of cervical, coeliac, and sacral ganglia, respectively. FDG-positive uptake was observed in 16.7%, 13.3%, and 2.5% of cervical, coeliac, and sacral ganglia, respectively. Cervical and coeliac ganglia had a higher rate of PSMA-positive uptake than sacral ganglia. Choline uptake was highest in coeliac ganglia followed by cervical and sacral ganglia. PSMA, choline or FDG uptake in LNM was all significantly higher than ganglia. ROC curve analysis revealed that at a 4.1 SUVmax cutoff of PSMA-PET, the sensitivity, specificity and accuracy of LNM identification was 88.4%, 97.9% and 96.2%, respectively. ROC curve analysis revealed that at a 2.35 SUVmax cutoff for choline-PET, the sensitivity, specificity, and accuracy of LNM identification was 95.0%, 92.6% and 93.0%, respectively. ROC curve analysis revealed that at a 2.55 SUVmax cutoff for FDG-PET, the sensitivity, specificity, and accuracy of LNM identification was 77.3%, 87.2%, and 81.9%, respectively. PSMA-, Choline- and FDG-positive ganglia are mainly band-shaped; most LNMs exhibited nodular and teardrop-shaped configuration.Conclusion68Ga-PSMA and 11C-choline uptake in ganglia was common, and FDG-positive ganglia were observed at lower frequency. Using 68Ga-PSMA, 11C-choline and 18F-FDG uptake and anatomic location and configuration, the differentiation of ganglia from adjacent LNM is feasible.

Purpose: Studies have indicated that PSMA-positive ganglia represent a diagnostic pitfall for nuclear medicine physicians. No studies have described choline and FDG uptake in ganglia, which may be a source of misdiagnosis. Herein, we described the percentage and uptake pattern of 68Ga-PSMA, 11C-choline and 18F-FDG PET/CT in ganglia and evaluated the heterogeneous metabolic patterns of ganglia to differentiate from lymph node metastases (LNM). Methods: Thirty-nine patients who underwent 11C-choline PET/CT and 120 patients who underwent 68Ga-PSMA PET/CT and 18F-FDG PET/CT were retrospectively analyzed. The prevalence of PSMA-positive, choline-positive and FDG-positive ganglia was determined, the SUVmax of ganglia in different locations were measured, and the configuration was described. The SUVmax cutoff of PSMA-PET, choline-PET and FDG-PET was determined by ROC curve analysis to differentiate ganglia from LNM. Results: 329 PSMA-positive ganglia were identified in 120 patients, 95 choline-positive ganglia were identified in 39 patients, and 39 FDG-positive ganglia were identified in 34 patients. PSMA-positive uptake was observed in 98.3%, 95.8%, and 80.0% of cervical, coeliac, and sacral ganglia, respectively. Choline-positive uptake was observed in 84.6%, 97.4%, and 61.5% of cervical, coeliac, and sacral ganglia, respectively. FDG-positive uptake was observed in 16.7%, 13.3%, and 2.5% of cervical, coeliac, and sacral ganglia, respectively. Cervical and coeliac ganglia had a higher rate of PSMA-positive uptake than sacral ganglia. Choline uptake was highest in coeliac ganglia followed by cervical and sacral ganglia. PSMA, choline or FDG uptake in LNM was all significantly higher than ganglia. ROC curve analysis revealed that at a 4.1 SUVmax cutoff of PSMA-PET, the sensitivity, specificity and accuracy of LNM identification was 88.4%, 97.9% and 96.2%, respectively. ROC curve analysis revealed that at a 2.35 SUVmax cutoff for choline-PET, the sensitivity, specificity, and accuracy of LNM identification was 95.0%, 92.6% and 93.0%, respectively. ROC curve analysis revealed that at a 2.55 SUVmax cutoff for FDG-PET, the sensitivity, specificity, and accuracy of LNM identification was 77.3%, 87.2%, and 81.9%, respectively. PSMA-, Choline- and FDG-positive ganglia are mainly band-shaped; most LNMs exhibited nodular and teardrop-shaped configuration. Conclusion: 68Ga-PSMA and 11C-choline uptake in ganglia was common, and FDG-positive ganglia were observed at lower frequency. Using 68Ga-PSMA, 11C-choline and 18F-FDG uptake and anatomic location and configuration, the differentiation of ganglia from adjacent LNM is feasible. [ABSTRACT FROM AUTHOR]

Objectives: The objective was to evaluate the diagnostic performance of surveillance11 C-choline positron emission tomography/computed tomography (PET/CT) for the detection of disease relapse in patients with a history of biochemically recurrent (BCR) prostate cancer (PCa) and prostate-specific antigen (PSA) ≤0.1 ng/ml.Materials and Methods: We included patients who had been treated for BCR PCa and had a surveillance11 C-choline PET/CT at serum PSA ≤0.1 ng/ml. Positive surveillance PET/CT was defined as a study that identified a new tracer-avid lesion or new tracer uptake in a previously treated lesion or both. Findings were confirmed against a composite radiologic-pathologic gold standard. Time to recurrence association analyses were performed for disease relapse risk with the use of Cox proportional hazards regression.Results: In total, 13 (12.1%) of the 107 patients had positive surveillance PET/CT scans, confirmed on pathologic assessment (n = 5) and subsequent imaging (n = 8). Among these 13 patients, ten had distant metastases, two had local recurrence, and one had both. Nine of the ten patients with metastases had oligometastatic disease defined as the presence of ≤3 metastases. Serum PSA became detectable again in only seven patients with positive surveillance PET/CT, after a mean interval from surveillance PET/CT of 292 days (range: 105-543 days). We identified an association of N stage with increased risk of recurrence (hazard ratio = 3.85; P = 0.036) although this was not significant after accounting for multiple testing.Conclusions: Surveillance11 C-choline PET/CT can detect early disease relapse at serum PSA ≤0.1 ng/ml in patients with a history of BCR PCa. [ABSTRACT FROM AUTHOR]

The importance of [11C]-choline as a PET/CT marker has been extensively described, although its production presents considerable technical difficulties. The main ones are short half-lives and the occurrence of dimethylformamide (DMF) as a residual solvent. While the losses resulting from the radionuclide decay can be minimised by shortening the duration of the process, the best solution for reducing the content of DMF is its elimination from the reaction environment. In the current work two methods are compared for [11C]-choline synthesis – a green chemistry approach (with ethanol as a green solvent) and a dry synthesis. The results were compared with each other and with those of the method based on DMF. The solid phase synthesis proved to be the most effective in total elimination of DMF, its final release was the highest, and the synthesis time was the shortest. The optimised synthesis led to the formation of the desired radiotracer with a high radiochemical yield (65% ±3%) in a short production time (12 min) and the residual precursor in the final product at the level of 1 µg/ml. 27% increase of the saturation yield was possible, which resulted in 9 GBq higher activity from 40 minutes of beaming. Each test batch passed all standard quality control requirements, and the levels of residual DMEA were below the limits that have been published in the last Pharmacopoeia monograph

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.

Purpose: The 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 Methods: Before 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. Results: The 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). Conclusion: P/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. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic efficacy of 11 C-choline PET/CT, neck ultrasonography, 99m Tc-MIBI dual-phase planar scintigraphy, and 99m Tc-MIBI SPECT/CT imaging in the diagnosis of primary hyperparathyroidism (PHPT). Methods: We conducted a retrospective analysis of 32 patients with PHPT who visited the Nuclear Medicine Department of Jilin University China-Japan Union Hospital between January 2019 and December 2022. All patients underwent 11 C-choline PET/CT, neck ultrasonography, 99m Tc-MIBI dual-phase planar scintigraphy, and 99m Tc-MIBI SPECT/CT examinations within two months before surgery. Sensitivity, specificity, positive predictive value, and negative predictive value of each imaging study were compared using postoperative pathology and follow-up results. Diagnostic efficacy was further analyzed using ROC curve analysis. Factors influencing on 99m Tc-MIBI imaging were also investigated. Results: A total of 35 lesions were resected in the 32 patients. The diagnostic sensitivity of 11 C-choline PET/CT, neck ultrasonography, 99m Tc-MIBI dual-phase planar scintigraphy, and 99m Tc-MIBI SPECT/CT was 88.2%, 52.9%, 58.8%, and 67.6%, respectively. Specificity was 96.8%, 95.7%, 96.8%, and 95.7%, respectively. Positive predictive values were 90.9%, 81.8%, 86.9%, and 85.2%, respectively, and negative predictive values were 95.7%, 84.9%, 86.7%, and 89.1%, respectively. The areas under the ROC curve (AUC) were 0.925, 0.743, 0.778, and 0.817, respectively. Among them, 11 C-choline PET/CT had higher sensitivity and AUC than other imaging studies (p<0.05), while specificity, positive predictive value, and negative predictive value were similar (p>0.05). The positive group in 99m Tc-MIBI SPECT/CT imaging had significantly larger lesion diameters than the negative group (P<0.05), while preoperative blood calcium and PTH showed no statistical differences (P>0.05). Conclusion: 11 C-choline PET/CT demonstrates superior preoperative diagnostic efficacy for PHPT compared to neck ultrasonography, 99m Tc-MIBI dual-phase planar scintigraphy, and 99m Tc-MIBI SPECT/CT. Lesion size may be the primary factor affecting the sensitivity of 99m Tc-MIBI imaging., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Abstract Background The aim of this study was to prospectively compare the detection rate of 68Ga-PSMA versus 11C-Choline in men with prostate cancer with biochemical recurrence and to demonstrate the added value of a tri-modality PET/CT-MRI system. Methods We analysed 36 patients who underwent both 11C-Choline PET/CT and 68Ga-PSMA PET/CT scanning within a time window of 1-2 weeks. Additionally, for the 68Ga-PSMA scan, we used a PET/CT-MRI (3.0 T) system with a dedicated shuttle, acquiring MRI images of the pelvis. Results Both scans were positive in 18 patients (50%) and negative in 8 patients (22%). Nine patients were positive with 68Ga-PSMA alone (25%) and one with 11C-Choline only (3%). The median detected lesion per patient was 2 for 68Ga-PSMA (range 0-93) and 1 for 11C-Choline (range 0-57). Tumour to background ratios in all concordant lesions (n = 96) were higher for 68Ga-PSMA than for 11C-Choline (110.3 ± 107.8 and 27.5 ± 17.1, mean ± S.D., for each tracer, respectively P = 0.0001). The number of detected lesions per patient was higher for 11C-Choline in those with PSA ≥ 3.3 ng/mL, while the number of detected lesions was independent of PSA levels for 68Ga-PSMA using the same PSA cut-off value. Metastatic pelvic lesions were found in 25 patients (69%) with 68Ga-PSMA PET/CT, in 18 (50%) with 11C-Choline PET/CT and in 21 (58%) with MRI (3.0 T). MRI was very useful in detecting recurrence in cases classified as indeterminate by means of PET/CT alone at prostate bed. Conclusions In patients with prostate cancer with biochemical recurrence 68Ga-PSMA detected more lesions per patient than 11C-Choline, regardless of PSA levels. PET/CT-MRI (3.0 T) system is a feasible imaging modality that potentially adds useful relevant information with increased accuracy of diagnosis.

Abstract Hybrid imaging plays a central role in the diagnosis and management of a wide range of malignancies at all stages. In this article, we review the most pertinent historical developments, emerging clinical applications of novel radiotracers and imaging technologies, and potential implications for training and practice. This includes an overview of novel tracers for prostate, breast, and neuroendocrine tumors, assessment of tumor heterogeneity, the concept of image-guided ‘biologically relevant dosing’, and theranostic applications. Recent technological advancements, including time-of-flight PET, PET/MRI, and ‘one-minute whole-body PET’, are also covered. Finally, we discuss how these rapidly evolving applications might affect current training curricula and how imaging-derived big data could be harnessed to the benefit of our patients.

Objective: Among different PET tracers, 18F-fludeoxyglucose (FDG) and 11C-choline are known to have a high tumor uptake correlated with a high mitotic index of tumor cells. Thus, the uptake of 18F-FDG and 11C-choline may be dependent on the cell cycle. In the present study, we examined the uptake of 18F-FDG and 11C-choline in cancer cell lines by cell cycle synchronization to clarify the biological properties of cancer cells with respect to each tracer.Methods: HeLa S3 Cells were synchronized by the double thymidine (TdR) block methods. 18F-FDG and 11C-choline were administered to synchronized cells, and the radioactivity per cell was measured to compare the cellular uptake of the tracers during S, G2/M, and G1 phases. Flow cytometry (FCM) was performed to measure the proportion of cells in G1, S, and G2/M phases. Furthermore, the levels of glucose transporter 1 (GLUT1) and choline transporter-like protein 1 (CTL1) in the cell were evaluated by FCM.Results: The uptake of 18F-FDG was the highest in S to G2/M phases, and markedly decreased in G1 phase. The uptake of 11C-choline reached its peak in G2/M, and decreased in G1 phase. The level of GLUT1 expression was similar to that of 18F-FDG uptake during the cell cycle, and the level of CTL1 expression was similar to that of 11C-choline uptake throughout the cell cycle.Conclusions: In this in vitro study, we demonstrated that 18F-FDG and 11C-choline had the highest uptake in S to G2/M phases and in G2/M phase, respectively, with a rapid decrease in G1 phase. These findings suggest that 18F-FDG and 11C-choline have a high accumulation in tumor cells with a high mitotic index. Furthermore, our study suggests that the expression of GLUT1 and CTL1 has cell cycle dependence, and the changes of 18F-FDG and 11C-choline accumulation seem to be caused by the above properties of these transporters. [ABSTRACT FROM AUTHOR]

Resumen Antecedentes y objetivos Comparar prospectivamente la tasa de detección de la PET/TC con 68Ga-DOTATATE versus 11C-colina en pacientes con cáncer de próstata en recaída bioquímica y evaluar in vivo la expresión de receptores de la somatostatina con el fin de planificar terapias dirigidas (177Lu-DOTATATE). Material y métodos Analizamos prospectivamente 64 pacientes con recaída bioquímica (mediana PSA: 4,25 ng/mL). Se realizó una PET/TC con 11C-colina y otra con 68Ga-DOTATATE. Se midió el SUVmáx en todas las lesiones. Se consideraron como patrón de referencia las imágenes correlativas, histopatología y/o seguimiento clínico y bioquímico. Resultados La tasa de detección global por paciente fue del 48,43% para 68Ga-DOTATATE y de 46,87% para 11C-colina. Los resultados fueron concordantes en 53 casos (82,81%). El SUV máximo de la 11C-colina fue significativamente mayor que el correspondiente al 68Ga-DOTATATE para todas las lesiones concordantes (n = 130): 6,17 (1,7-15,5) versus 4,38 (1,37-26,7), mediana (rango), para cada radiotrazador, respectivamente (P < 0,0001). Los valores por paciente de sensibilidad y especificidad fueron los mismos para ambas técnicas: 0,82 (0,65-0,93) y 0,9 (0,73-0,98), respectivamente. Aunque la diferencia no fue estadísticamente significativa, la sensibilidad fue menor para pacientes con niveles de PSA inferiores: 0,63 vs. 0,89; p = 0,13. Se encontró una correlación significativa entre el SUVmáx de ambos trazadores (r = 0,41, n = 130, p < 0,0001). Conclusiones La PET/TC con 68Ga-DOTATATE y la PET/TC con 11C-colina parecen poseer alta capacidad de detección de lesiones patológicas en la evaluación de los pacientes con cáncer de próstata en recaída bioquímica. Se necesitan más estudios con el fin de probar el posible valor clínico complementario de estas técnicas PET/TC, y para el 68Ga-DOTATATE para la potencial planificación de terapias mediadas por los receptores de somatostatina (177Lu-DOTATATE). Abstract Background and objectives To prospectively compare the detection rate of 68Ga-DOTATATE versus 11C-choline PET/CT in patients with prostate cancer in biochemical relapse, and to evaluate somatostatin receptor expression in vivo to plan targeted therapies (177Lu-DOTATATE). Material and methods We prospectively analysed 64 patients with biochemical relapse (median PSA: 4.25 ng/mL). A PET/CT was performed with 11C-choline, and another with 68Ga-DOTATATE. The SUVmax was measured in all lesions. The correlative images, histopathology and/or clinical and biochemical follow-up were taken as the reference standard. Results The overall detection rate per patient was 48.43% for 68Ga-DOTATATE and 46.87% for 11C-choline. The results were concordant in 53 cases (82.81%). The maximum SUV of 11C-choline was significantly higher than that of 68Ga-DOTATATE for all the concordant lesions (n=130): 6.17 (1.7-15.5) versus 4.38 (1.37-26.7), median (range) for each radiotracer, respectively (p <.0001). The sensitivity and specificity values per patient were the same for both techniques: 0.82 (0.65-0.93) and 0.9 (0.73-0.98), respectively. Although the difference was not significant, the sensitivity was lower in patients with lower PSA levels: 0.63 vs. 0.89; p =.13. A significant correlation was found between the SUVmax of both tracers (r = 0.41, n = 130, p <.0001). Conclusions 68Ga-DOTATATE PET/CT and 11C-choline PET/CT seem to have a high capacity to detect pathological lesions in the assessment of patients with prostate cancer with biochemical relapse. Further studies are required to test the potential complementary value of these PET/CT techniques, and to evaluate the potential role of 8Ga-DOTATATE for planning somostatin receptor-mediated therapies (177Lu-DOTATATE). [ABSTRACT FROM AUTHOR]

The importance of [11C]-choline as a PET/CT marker has been extensively described, although its production presents considerable technical difficulties. The main ones are short half-lives and the occurrence of dimethylformamide (DMF) as a residual solvent. While the losses resulting from the radionuclide decay can be minimised by shortening the duration of the process, the best solution for reducing the content of DMF is its elimination from the reaction environment. In the current work two methods are compared for [11C]-choline synthesis - a green chemistry approach (with ethanol as a green solvent) and a dry synthesis. The results were compared with each other and with those of the method based on DMF. The solid phase synthesis proved to be the most effective in total elimination of DMF, its final release was the highest, and the synthesis time was the shortest. The optimised synthesis led to the formation of the desired radiotracer with a high radiochemical yield (65% ±3%) in a short production time (12 min) and the residual precursor in the final product at the level of 1 μg/ml. 27% increase of the saturation yield was possible, which resulted in 9 GBq higher activity from 40 minutes of beaming. Each test batch passed all standard quality control requirements, and the levels of residual DMEA were below the limits that have been published in the last Pharmacopoeia monograph. [ABSTRACT FROM AUTHOR]

The field of multiple myeloma (MM) imaging has evolved. The International Myeloma Working Group recently recommended performing 18F-fluorodeoxyglucose glucose (18FDG) positron emission tomography/computed tomography (PET/CT) with the aim of staging MM patients at baseline and evaluating response to therapy. Novel oncological radiotracers such as 11C-Choline and 18F-Fluorocholine, have been studied in comparison with 18FDG, mostly in MM patients presenting with refractory disease or suspected relapse. Choline-based tracers may overcome some limitations of 18FDG, which include a lack of sensitivity in depicting skull lesions and the fact that 10% of MM patients are FDG-negative. The majority of MM lesions display a higher uptake of Choline than FDG. Also, in many situations, Choline may offer better lesion visualization, with a higher tumor to background ratio; however, various patterns of Choline and FDG uptake have been observed in MM and some limitations, notably as regards liver lesions, should be recognized. Overall, Choline may provide additional detection of up to 75% more lesions. This article aims to provide a comprehensive review of the potential role of Choline in multiple myeloma, as compared to FDG, encompassing Choline physiopathology as well as data from clinical studies.

Purpose: Previous studies in prostate cancer (PCa) patients tried to correlate the onset of local recurrence (LR) with the development of distant metastases and formulated, based on theoretical and experimental data, hypotheses linking the two events. We aimed to address this issue with 11C-choline positron emission tomography/computed tomography (PET/CT).Methods: This retrospective study included 491 PCa patients previously treated with radical prostatectomy who had undergone 11C-choline PET/CT owing to biochemical failure. Further inclusion criteria were availability of clinical and pathological variables for survival analysis. Statistical significance was taken at P < 0.05.Results: Seventy-two patients (14.7%) had evidence of LR at 11C-choline PET/CT. The frequency of LR increased from 13.8% in the interval 0-4 years after prostatectomy, to 23.9% in the 12-16-year interval (P = 0.080). On the contrary, the frequency of lymph node metastases (overall rate in the 0-16 years interval after prostatectomy: 26.3%) and of bone metastases (overall rate: 13.8%) decreased significantly over time. Kaplan-Meier curves showed no significant group difference in the rates of lymph node or bone metastases between patients with LR and patients without LR. LR significantly predicted PCa-specific survival at univariate analysis, but the statistical significance was lost at multivariate analysis.Conclusion: We found no differences in the rates of lymph node and bone metastases between patients with and without LR. An inverse time-dependent trend was observed in the frequency of LR on one side and of lymph node and bone metastases on the other side. These findings were discussed in relation to previous theories linking LR to distant metastases and our study design. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to evaluate the accuracy of unenhanced whole-body MRI, including whole-body Diffusion Weighted Imaging (DWI), used as a diagnostic modality to detect pathologic lymph nodes and skeletal metastases in patients with prostate cancer (PCa) undergoing restaging after primary treatment. PATIENTS AND METHODS: 152 male patients with biochemical recurrence after radical prostatectomy (RP) or external beam radiation therapy (EBRT) underwent MRI at a 1.5 Tesla magnet with whole spinal sagittal T2-weighted, sagittal T1- weighted, sagittal STIR images, axial T1 and T2- weighted and STIR images of the pelvis and whole-body. 18Fcholine-PET/CT exam was used as the reference standard. RESULTS: MRI protocol including whole-body combined T1-weighted+T2-weighted+STIR+DWI showed a sensitivity (Se) of 99%, a specificity (Spe) of 98%, a positive predictive value (PPV) of 98%, a negative predictive value (NPV) of 96%, an accuracy of 98% and an area under the receiver operating characteristic curve (AUC) of 0.971 for identification of bone metastatic lesion. The same protocol, displayed a Se of 98%, a Spe of 99%, a PPV of 97%, a NPV of 98%, an accuracy of 98 % and an AUC of 0.960 in the detection of pathologic lymph nodes. CONCLUSIONS: Unenhanced whole-body MRI, including whole-body-DWI, is an accurate and cost-effective diagnostic tool which is able to detect lymph node involvement and bone metastases in patients with biochemically recurrent PCa after RP or EBRT. Thanks to its lack of ionizing radiation, excellent soft tissue contrast, high spatial resolution, no need of contrast agent, high Se and Spe, it could play a role in the restaging procedure of such patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We present the first case of salvage retroperitoneal lymph node dissection based on the results of 18F-FACBC PET/CT performed for a prostate-specific antigen relapse after radical prostatectomy. The patients underwent 11C-choline PET/CT, which turned out negative, while 18F-FACBC PET/CT visualized two lymph node metastases confirmed at pathological examination. Preliminary clinical reports showed an improvement in the detection rate of 20-40% for 18F-FACBC in comparison with 11C-choline, rendering the 18F-FACBC the potential radiotracer of the future. Salvage surgery for prostate cancer is a fascinating but controversial approach. New diagnostic tools may improve its potential by increasing the assessment and the selection of the patients. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We present the first case of salvage radiotherapy based on the results of 18F-FACBC PET/CT performed for a PSA relapse after radical prostatectomy. The patients underwent 11CCholine PET/CT and multiparametric MRI that were negative while 18F-FACBC PET/CT visualized a suspected local relapse confirmed by transrectal ultrasound-guided biopsy. No distant relapse was detected. Thus the patient was submitted to salvage radiotherapy in the prostatic fossa. After 20 months of follow-up, the PSA was undetectable and 18F-FACBC PET/CT was negative. Salvage radiotherapy after surgery, provided that it is administered at the earliest evidence of the biochemical relapse, may improve cancer control and favourably influence the course of disease as well as the adjuvant approach. New imaging techniques may increase the efficacy of the salvage radiotherapy thus helping in the selection of the patients. Preliminary clinical reports showed an improvement in the detection rate of 20-40% of 18F-FACBC in comparison with 11C-Choline for the detection of disease relapse after radical prostatecomy, rendering the 18F-FACBC the potential radiotracer of the future for prostate cancer.

Purpose: The aim of this study was to evaluate the potential usefulness of whole-body C-choline PET/CT in the re-staging of prostate cancer (PC) patients previously treated with radical prostatectomy (RP), who presented a mild increase of prostate-specific antigen (PSA) <1.5 ng/ml (early biochemical relapse) during follow-up (FU). Methods: We evaluated 102 consecutive patients (mean age = 68 years, range = 54-82 years) previously treated with RP and who presented during FU a mild increase of trigger PSA serum levels <1.5 ng/ml: mean 0.86 ± 0.40 ng/ml (range 0.2-1.5) and median 0.93 ng/ml (range 0.67-1.10). In this patient series C-choline PET/CT was used as the first imaging examination at the time of the detection of a mild serum PSA increase <1.5 ng/ml. C-Choline PET/CT was performed following standard procedures in our centre. At the time of PET/CT, 86 patients were not receiving any pharmacologic treatment, while 16 were under anti-androgenic therapy. Positive PET findings were validated by: (a) transrectal ultrasound (TRUS)-guided biopsy in cases of local recurrence, (b) surgical lymphadenectomy, (c) other imaging procedures or (d) FU lasting for at least 12 months. Univariate and multivariate analyses were used to evaluate the following variables: age, TNM staging, Gleason score, time from RP to the biochemical relapse, anti-androgen therapy at the time of C-choline PET/CT scan, trigger PSA value and PSA kinetics, i.e. PSA doubling time (PSAdt) and PSA velocity (PSAvel), in order to assess the significant predictive factors related to the findings of a positive C-choline PET/CT scan. Results: Overall, C-choline PET/CT showed positive findings in 29 of 102 patients (28% of cases). In detail, C-choline PET/CT detected: local relapse in 7 patients, bone metastases in 13 patients (4 single and 9 multiple) and lymph node metastases in 9 patients (6 single and 3 multiple). Positive PET findings were validated by: (a) TRUS-guided biopsy in 7 patients with local recurrence, (b) surgery and lymphadenectomy in 3 patients, (c) other targeted imaging procedures (MR or bone scan) in 5 patients and (d) clinical FU lasting a minimum of 12 months and including also a contrast-enhanced CT (CECT), an MR, a bone scan and a repeated C-choline PET/CT in 14 patients. Age, time to biochemical relapse (TTR), initial T staging, Gleason score and trigger PSA were not statistically significant in predicting a positive C-choline PET/CT scan both at univariate and multivariate analysis. Instead, PSA kinetics (PSAdt and PSAvel), N status and anti-androgenic therapy at the time of PET scan were statistically significant predictive factors at univariate analysis. Of note, only PSAdt and initial N status were found to be significant and independent predictive factors at multivariate analysis. The mean PSAdt in PET-positive patients was 4.34 months (SD 2.82) while in PET-negative patients it was 13.30 months (SD 9.75) ( p = 0.0001). The optimal threshold for PSAdt established by receiver-operating characteristic (ROC) analysis was 7.25 months (AUC 0.85; 95% confidence interval 0.77-0.91) providing 93% sensitivity, 74% specificity, 60% positive predictive value and 96% negative predictive value. Conclusion: In our study, C-choline PET/CT was able to detect recurrent disease in 28% of the patients with mild biochemical relapse characterized by very low trigger PSA levels (PSA <1.5 ng/ml). Very interestingly C-choline PET/CT detected distant unexpected metastases in 21% of the patients. At multivariate statistical analysis only PSAdt and node status were shown to be significant and independent predictive factors for positive C-choline PET/CT. Therefore, C-choline could be suggested to be performed early during initial biochemical relapse in patients presenting with fast PSA kinetics. The early detection of the site of recurrence could lead to a prompt instauration of the most appropriate treatment, i.e. local surgery or radiation treatment vs systemic treatment. In this view, one of the main advantages should be the avoidance of unnecessary local radiotherapy in those patients showing distant metastasis at C-choline PET/CT. [ABSTRACT FROM AUTHOR]

Purpose Inflamed atherosclerotic plaques may rupture and cause acute myocardial infarction, stroke and other thrombotic events. Early detection of these unstable plaques could, in many cases, prevent such potentially fatal events. 11C-choline or 18F-labelled choline derivatives for visualizing the synthesis of phospholipids, are promising markers of plaque inflammation with potential advantages over 18FFDG. Their potential for plaque characterization in humans is, however, unclear. In this study the prevalence and distribution of 11C-choline uptake in the aortic and common carotid arterial walls of elderly male patients was evaluated with combined PET/CT. Additionally, the localization of radiotracer uptake and calcification was correlated in various vessel segments. Methods Image data from 93 consecutive male patients between 60 and 80 years old who had undergone whole-body 11C-choline PET/CT assessment for prostate cancer were evaluated retrospectively. 11C-choline uptake and calcification were analysed qualitatively and semiquantitatively and compared. Results 11C-choline uptake was found in 95% of patients, calcification in 94% throughout all vessel segments. In 6% of the patients radiotracer uptake was colocalized with calcifications, whereas less than 1% of calcification sites showed increased radiotracer uptake. Conclusion Both 11C-choline uptake and calcification in the aortic and common carotid arterial walls are common in elderly men. Radiotracer uptake and calcification are, however, only rarely colocalized. 11C-choline has the potential to provide information about atherosclerotic plaques independent of calcification measurement. [ABSTRACT FROM AUTHOR]

The role of molecular imaging in initial evaluation of men with presumed or established diagnosis of prostate cancer and work up of biochemical recurrence and metastatic disease is rapidly evolving due to superior diagnostic performance compared to anatomic imaging. However, variable tumor biology and expression of transmembrane proteins or metabolic alterations poses a challenge. We review the evidence and controversies with emphasis on emerging PET radiopharmaceuticals and experience on clinical utility of PET/CT and PET/MRI in diagnosis and management of prostate cancer. [ABSTRACT FROM AUTHOR]

The patient population with a rising prostate specific antigen (PSA) post-therapy with no evidence of disease on standard imaging studies currently represents the second largest group of prostate cancer patients. Little information is still available regarding the specificity and sensitivity of positron emission tomography (PET) tracers in the assessment of early biochemical recurrence. Ideally, PET imaging would allow one to accurately discriminate between local vs nodal vs distant relapse, thus enabling appropriate selection of patients for salvage local therapy. The vast majority of studies show a relatively poor yield of positive scans with PSA values <4 ng ml−1. So far, no tracer has been shown to be able to detect local recurrence within the clinically useful 1 ng ml−1 PSA threshold, clearly limiting the use of PET imaging in the post-surgical setting. Preliminary evidence, however, suggests that 11C-choline PET may be useful in selecting out patients with early biochemical relapse (PSA <2 ng ml−1) who have pelvic nodal oligometastasis potentially amenable to local treatment. The role of PET imaging in prostate cancer is gradually evolving but still remains within the experimental realm. Well-conducted studies comparing the merits of different tracers are needed.Prostate Cancer and Prostatic Diseases (2008) 11, 121–128; doi:10.1038/sj.pcan.4501028; published online 8 January 2008 [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate and compare the role of 11C-choline positron emission tomography (PET) and transrectal ultrasonography (TRUS) in the preoperative staging of clinically localized prostate cancer. PATIENTS AND METHODS Fifty-five consecutive patients with biopsy-confirmed prostate cancer had TRUS and 11C-choline PET as a part of their clinical staging programme before radical retropubic prostatectomy (RP). The PET images were prospectively interpreted by a consensus decision of two nuclear medicine physicians and one radiologist with special expertise in the field. The TRUS was done by one experienced urologist. The criteria evaluated prospectively in each patient were extracapsular extension (ECE), seminal vesicle invasion (SVI) and bladder neck invasion (BNI). The results were compared with the histopathological findings after RP. RESULTS At pathology, 32 patients were classified pT2, 16 as pT3a and three had pT3b lesions. In four patients the histopathological examination showed pT4 with BNI. The overall accuracy of PET in defining local tumour stage (pT2 and pT3a−4) was 70%; the overall accuracy by TRUS was 26%. PET was more sensitive than TRUS for detecting ECE (pT3a) and SVI (pT3b) in advanced stages, and in pT4 stages. The sensitivity and positive predictive value (PPV) (95% confidence interval) in stages pT3a–pT4 for PET were 36 (17–59)% and 73 (39–89)%. The sensitivity and PPV in stages pT3a–pT4 for TRUS were 14 (3–35)% and 100 (29–100)%. CONCLUSIONS 11C-choline PET and TRUS tended to understage prostate cancer. This series shows the current limited value of TRUS and PET for making treatment decisions in patients with clinically localized prostate cancer, especially if a nerve-sparing RP is considered. Treatment decisions should not be based on TRUS and 11C-choline PET findings alone. In future studies, the combination of metabolic and anatomical information of PET and endorectal magnetic resonance imaging should be evaluated, as this might optimize the preoperative staging in prostate cancer. [ABSTRACT FROM AUTHOR]

The value and limitations of 11C-choline PET and PET/CT for the detection of prostate cancer remain controversial. The aim of this study was to investigate the diagnostic efficacy of 11C-choline PET and PET/CT in a large group of patients with suspected prostate cancer. Fifty-eight patients with clinical suspicion of prostate cancer underwent 11C-choline PET (25/58, Siemens ECAT Exact HR+) or PET/CT (33/58, Philips Gemini) scanning. On average, 500 MBq of 11C-choline was administered intravenously. Studies were interpreted by raters blinded to clinical information and other diagnostic procedures. Qualitative image analysis as well as semiquantitative SUV measurement was carried out. The reference standard was histopathological examination of resection specimens or biopsy. Prevalence of prostate cancer in this selected patient population was 63.8% (37/58). 11C-choline PET and PET/CT showed a sensitivity of 86.5% (32/37) and a specificity of 61.9% (13/21) in the detection of the primary malignancy. With regard to metastatic spread, PET showed a per-patient sensitivity of 81.8% (9/11) and produced no false positive findings. Based on our findings, differentiation between benign prostatic changes, such as benign prostatic hyperplasia or prostatitis, and prostate cancer is feasible in the majority of cases when image interpretation is primarily based on qualitative characteristics. SUVmax may serve as guidance. False positive findings may occur due to an overlap of 11C-choline uptake between benign and malignant processes. By providing functional information regarding both the primary malignancy and its metastases, 11C-choline PET may prove to be a useful method for staging prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To establish the effects of Na+/Ca2+ exchanger (NCX) blockers on 2-[18F]fluoro-2-deoxy-d-glucose (18FDG) and 11C-choline accumulation in different cancer cells. Methods: The tumor cells were incubated with NCX inhibitors, and the uptakes of 18FDG and 11C-choline were measured. Flow cytometric measurements of intracellular Ca2+ and Na+ concentrations were carried out. The presence of the NCX antigen in the cancer cells was proved by Western blotting, flow cytometry and confocal laser scanning microscopy. Results: The NCX is expressed at a noteworthy level in the cytosol and on the cytoplasmic membrane of the examined cells. Incubation of the cells with three chemically unrelated NCX blockers (bepridil, KB-R7943 or 3′,4′-dichlorobenzamil hydrochloride) resulted in an increase in the intracellular Ca2+ concentration, with a simultaneous decrease in the intracellular Na+ concentration. The treatment with the NCX inhibitors increased the energy consumption of the tumor cells by 50–100%. Thapsigargin abolished the NCX-induced 18FDG accumulation in the cells. The NCX blockers applied decreased the 11C-choline accumulation of all the investigated cancer cells by 60–80% relative to the control. Conclusion: A possible masking effect of NCX medication must be taken into consideration during the diagnostic interpretation of PET scans. [Copyright &y& Elsevier]