We evaluated the potential of 18F-fluoromethyldimethyl-2-hydroxyethyl-ammonium (FCH) PET/CT in the detection of recurrent disease or distant metastases and correlated its diagnostic accuracy with prostate-specific antigen (PSA) levels in prostate cancer patients with biochemical evidence of recurrence. Furthermore, the influences of androgen deprivation therapy (ADT) and its duration on 18F-FCH PET were assessed in this study. Methods: This prospective study included 250 prostate cancer patients with PSA relapse who underwent 18F-FCH PET/CT. At the time of 18F-FCH PET/CT imaging, the mean PSA level was 46.9 ± 314.7 ng/mL and 55.2% (138/250) of patients were receiving ADT. Overall, ADT was performed on 67.2% (168/250) of patients after initial treatment. Imaging was performed on an integrated PET/CT system. Acquisition started 1 min after intravenous injection of 18F-FCH (4.07 MBq/kg of body weight) with dynamic PET images in the pelvic region during 8 min (1 min/frame) followed by a static semi–whole-body acquisition. The final diagnosis of positive PET lesions was based on histopathology or a consensus of clinical findings, additional imaging, or follow-up imaging modalities. Results:18F-FCH PET/CT was able to correctly detect malignant lesions in 74% (185/250) of patients but was negative in 26% (65/250). In 28% of patients, only 1 lesion was detected (69/250); from these, 65.2% (45 patients) had a local recurrence, 18.8% (13 patients) a single lymph node, and 15.9% (11 patients) a solitary bone metastasis. The sensitivity of the 18F-FCH PET was significantly higher (P = 0.001) in patients with ongoing ADT (85%; confidence interval, 80%–91%) than in patients without ADT (59.5%; confidence interval, 50%–69%). 18F-FCH PET sensitivity was 77.5%, 80.7%, 85.2%, and 92.8% for the trigger PSA levels of more than 0.5, 1.0, 2.0, and 4.0 ng/mL, respectively. Scan sensitivity was 33% in patients with a trigger PSA level of less than 0.3 ng/mL and 77% in patients with a trigger PSA level of greater than 0.3 ng/mL, respectively (P = 0.001). Using a binary logistic regression analysis model, we showed trigger PSA and ADT to be the only significant predictors of positive PET findings. Conclusion:18F-FCH PET/CT proved its potential as a noninvasive 1-stop diagnostic modality enabling us to correctly detect occult disease in 74% of patients and to differentiate localized from systemic disease. In patients with biochemical recurrence, it also guides to an optimal treatment approach after initial treatment. Trigger PSA and ADT are the 2 significant predictors of 18F-FCH–positive PET lesions. ADT seems not to impair 18F-FCH uptake in hormone-refractory prostate cancer patients.

272 Objectives The diagnostic potential of PET/CT imaging with BAY1075553 ((2RS,4S)-2-[18F]Fluoro-4-phosphonomethyl-pentanedioic acid), a novel PET tracer with potential to bind with prostate-specific membrane antigen (PSMA), is compared to 18F - Fluorcholine (FCH) in prostate cancer. Methods 12 patients (9 primary staging, 3 Re-staging) with proven prostate cancer were included into this study. The mean PSA in the primary staging and restaging groups was 21.5± 12 ng/ml and 73.6 ± 33 ng/ml, respectively. The median Gleason score was of 8 in both groups. Acquisition started 30 seconds post intravenous injection of 300 MBq with dynamic PET images in the pelvic region during 12 minutes Static semi - whole body was performed immediately after the dynamic acquisition. Radical prostatectomy and ePLND was performed in the primary staging patients. Results In the prostate gland, there was a correlation between detected lesions by means of both imaging modalities and histopathological results. The mean SUVmax in the prostate gland was higher on FCH PET (6.95±1.6) than that on BAY1075553 PET (5.6±2.4), p=ns. FCH PET was able to detect a higher number of positive LNs compared to BAY1075553 PET. There was a correlation between both modalities in the detection of bone metastases, however, BAY1075553 could not detect a bone-marrow metastasis found in 1 patient. Furthermore, degenerative bone lesions showed intensive uptake of BAY1075553. Conclusions PET/CT using BAY1075553 was able to detect prostate cancer in patients with primary and advanced disease. However, PET/CT using FCH showed superior results compared to BAY1075553 in particular with respect to detection of LN and bone-marrow metastases

1125 Objectives Animal studies showed increased uptake of 18F-labeled BAY1075553 (2RS,4S)-2-[18F]Fluoro-4-phosphonomethyl-pentanedioicacid) in prostate cancer cells expressing prostate-specific membrane antigen. The aim of this study was to evaluate the safety, tolerability and biodistribution of this novel PET-tracer. Methods 12 prostate cancer patients were included into this study. All patients were clinically monitored from 24 hrs before to 5-8 days after tracer administration including physical examination, ECG, laboratory parameters of different organs and documentation of adverse events. PET acquisition started 30 sec. post i.v. injection of 300 MBq BAY1075553 with dynamic PET images in the pelvic region followed by semi-whole body acquisition. Results Safety data showed no relevant changes in the sequential blood values, ECGs, urine testing or physical examination up to 5 - 8 days after i.v. administration of BAY 1075553. Physiological BAY 1075553 uptake was observed in salivary glands and urinary tract. Intensive tracer accumulation was noticed in the urinary bladder. In general, remarkable tracer uptake was seen in degenerative bone lesions as well as in sclerotic vessels. Liver, pancreas, spleen, gastrointestinal tract and bone marrow showed no noticeable physiological uptake. Conclusions The results of this study showed that PET/CT imaging with BAY1075553 was safe and well tolerated. However, early renal excretion and intensive tracer accumulation in the urinary tract as well as non-specific increased tracer uptake in degenerative bone lesions could be the main limitations when using this radio tracer for staging and re-staging of prostate cancer patients. Details regarding the tumor uptake of BAY1075553 will be described in a separate abstract

[11C]Lithium trimethylsilyl ynolate was characterized to be a new precursor in carbon-11 chemistry. It was obtained from [11C]carbon monoxide and lithiated silyldiazomethane. The new precursor might be of high potential for the incorporation of carbon 11 into heterocyclic ring systems for which labeling methods are not well developed. More examples will certainly follow if other researchers will apply this useful method.

Objectives: With respect to the broad application of [F-18-methyl]fluorocholine (FCH), there is a need for a safe, but also efficient and convenient way for routine quality control of FCH. Therefore, a GC- method should be developed and validated which allows the simultaneous quantitation of all chemical impurities and residual solvents such as acetonitrile, ethanol, dibromomethane and N,N-dimethylaminoethanol.Methods: Analytical GC has been performed with a GC-capillary column Optima 1701 (50 mx0.32 mm), and a pre-column deactivated capillary column phenyl-Sil (10 mx0.32) in line with a flame ionization detector (FID) was used. The validation includes the following tests: specificity, range, accuracy, linearity, precision, limit of detection (LOD) and limit of quantitation (LOQ) of all listed substances.Results: The described GC method has been successfully used for the quantitation of the listed chemical impurities. The specificity of the GC separation has been proven by demonstrating that the appearing peaks are completely separated from each other and that a resolution R >= 1.5 for the separation of the peaks could be achieved. The specified range confirmed that the analytical procedure provides an acceptable degree of linearity, accuracy and precision. For each substance, a range from 2% to 120% of the specification limit could be demonstrated. The corresponding LOD values were determined and were much lower than the specification limits.Conclusions: An efficient and convenient GC method for the quality control of FCH has been developed and validated which meets all acceptance criteria in terms of linearity, specificity, precision, accuracy, LOD and LOQ. (C) 2011 Elsevier Inc. All rights reserved.

464 Objectives With respect to the broad application of [18F-methyl]fluorocholine(FCH)and its ungoing process of marketing authorisation, there is a need for a safe, but also efficient and convenient way of routine quality control of FCH since no monograph is currently available for radiolabelled choline derivatives. Therefore, a GC- method should be developed and validated which allows the simultaneous quantitation of all chemical impurities and residual solvents as acetonitrile, ethanol, dibromomethane and DMAE. Methods Analytical GC has been performed with a GC-capillary column Optima 1701 (50 m x 0.32 mm) and a deactivated capillary pre-column phenyl-Sil (10 m x 0.32) in row with a flame ionisation detector (FID. The validation includes the following tests: specificity, range, accuracy, linearity, precision, limit of detection (LOD) and limit of quantification (LOQ) of all listed substances. Results The described GC-method has been successfully used for the quantitation of the listed chemical impurities. The specificity of the GC-separation has been proved by demonstrating that the appearing peaks are completely separated from each other and a resolution R ≥ 1,5 for the separation of the peaks could be achieved. The specified range derived from linearity studies confirmed that the analytical procedure provides an acceptable degree of linearity, accuracy and precision when applied to samples containing amounts of analyte within the specified range. For each substance a range from the LOD until 110-120 % of the specification limit could be demonstrated. The LOD and LOQ were determined and both values were much lower than the specification limit for all substances: ethanol (17.6 µg/ 61.6 µg), DMAE (1.7 µg/ 5.1 µg), acetonitrile (19.6 µg/ 63.4 µg)and dibromomethane (2.4 µg/ 7.1 µg). Conclusions An efficient and convenient GC-method for the quality control of FCH has been developed and validated meeting all acceptance criteria in terms of linearity, specificity, precision, accuracy as well as LOD and LOQ

1913 Objectives To evaluate the potential of 18F fluoromethylcholine (FCH) PET/CT in the assessment of suspected recurrent prostate cancer in patients with biochemical evidence of recurrence and to correlate its diagnostic accuracy with PSA levels. Methods This study included 240 prostate cancer patients at PSA relapse after initial treatment who had undergone FCH PET/CT for the evaluation of recurrent disease. The mean PSA level was 41.2±319.5 ng/ml. Hormonal treatment(HT) was performed in 151(63%) cases after initial treatment. Imaging was performed on an integrated PET/CT system. Acquisition started 1 minute post intravenous injection of FCH (4Mbq/kg/bw) with dynamic PET images in the pelvic. Static acquisition from thigh to the base of skull was performed 10 min post injection, respectively. The final diagnosis of positive PET lesions was based on histopathological findings or a consensus based on clinical findings, additional imaging modalities and follow-up imaging modalities with a mean time interval of 5.3 months. Results FCH PET/CT was able to correctly detect malignant lesions in 160(66%) patients. The mean PSA level at the time of imaging was 60.3±389.0 ng/ml in patients with positive FCH PET/CT compared to 2.3±3.5 ng/ml in patients with negative FCH PET/CT studies (P=0.06). Although the finding does not reach statistical significance;however, there is a clear trend toward higher PSA levels with positive FCH results. FCH PET/CT were positive in 90.8% of patients with PSA levels ≥4.0 ng/ml while it was 42.9% in patients with PSA levels Conclusions Our data suggest that FCH PET/CT can reliably detect recurrent disease in prostate cancer patients especially in case of PSA level ≥2.5 ng/ml

PURPOSE:To prospectively evaluate the potential value of fluorocholine (FCH) positron emission tomography (PET)/computed tomography (CT) in the preoperative staging of patients with prostate cancer who had intermediate or high risk of extracapsular disease. MATERIALS AND METHODS:Institutional review board approval and written informed consent were obtained. Overall, 132 patients with prostate cancer (mean age, 63 years +/- 7 [standard deviation]) were enrolled between October 2003 and June 2008. Two patients were subsequently excluded. In 111 patients, radical prostatectomy with extended pelvic lymph node (LN) dissection was performed. Patients were categorized into groups with intermediate (n = 47) or high (n = 83) risk of extracapsular extension on the basis of their Gleason scores and prostate specific antigen levels. Imaging was performed with an integrated PET/CT system after injection of 4.07 MBq FCH per kilogram of body weight with acquisition of dynamic images in the pelvis and whole-body images. Statistical analysis was performed on a per-patient basis. RESULTS:Significant correlation was found between sections with the highest FCH uptake and sextants with maximal tumor infiltration (r = 0.68; P = .0001). Overall, 912 LNs were histopathologically examined. A per-patient analysis revealed the sensitivity, specificity, and positive and negative predictive values of FCH PET/CT in the detection of malignant LNs were 45%, 96%, 82%, and 83%, respectively. For LN metastases greater than or equal to 5 mm in diameter, sensitivity, specificity, and positive and negative predictive values were 66%, 96%, 82%, and 92%, respectively. In 13 patients, 43 bone metastases were detected. Early bone marrow infiltration was detected with only FCH PET in two patients. FCH PET/CT led to a change in therapy in 15% of all patients and 20% of high-risk patients. CONCLUSION:FCH PET/CT could be useful in the evaluation of patients with prostate cancer who are at high risk for extracapsular disease, and it could be used to preoperatively exclude distant metastases. SUPPLEMENTAL MATERIAL:http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090413/-/DC1.

The purpose of this prospective study was to compare the value of DOPA PET-CT with FDG PET-CT in the detection of malignant lesions in patients with medullary thyroid carcinoma (MTC). Twenty-six consecutive patients (10 men, 16 women, mean age 59 +/- 14 years) with elevated calcitonin levels were evaluated in this prospective study. DOPA and FDG PET-CT modalities were performed within a maximum of 4 weeks (median 7 days) in all patients. The data were evaluated on a patient- and lesion-based analysis. The final diagnosis of positive PET lesions was based on histopathological findings and/or imaging follow-up studies (i.e., DOPA and/or FDG PET-CT) for at least 6 months (range 6-24 months). In 21 (21/26) patients at least one malignant lesion was detected by DOPA PET, while only 15 (15/26) patients showed abnormal FDG uptake. DOPA PET provided important additional information in the follow-up assessment in seven (27%) patients which changed the therapeutic management. The patient-based analysis of our data demonstrated a sensitivity of 81% for DOPA PET versus 58% for FDG PET, respectively. In four (4/26) postoperative patients DOPA and FDG PET-CT studies were negative in spite of elevated serum calcitonin and CEA levels as well as abnormal pentagastrin tests. Overall 59 pathological lesions with abnormal tracer uptake were seen on DOPA and/or FDG PET studies. In the final diagnosis 53 lesions proved to be malignant. DOPA PET correctly detected 94% (50/53) of malignant lesions, whereas only 62% (33/53) of malignant lesions were detected with FDG PET. DOPA PET-CT showed superior results to FDG PET-CT in the preoperative and follow-up assessment of MTC patients. Therefore, we recommend DOPA PET-CT as a one-stop diagnostic procedure to provide both functional and morphological data in order to select those patients who may benefit from (re-)operation with curative intent as well as guiding further surgical procedures.

F-18 fluor choline-positron emission tomography/computed tomography (FCH-PET/CT) has emerged as a new diagnostic tool for the imaging of prostate cancer. In this study, we have evaluated the potential role of FCH-PET/CT for the assessment of bone metastases in patients with prostate cancer. Furthermore, we assessed the pattern of metabolic uptake by FCH in relation to morphologic changes on CT.

597 Objectives: F-18 Fluoride PET-CT is the most sensitive imaging modality for detection of malignant bone involvement. The aim of this study was to examine if semiquantitative analysis by SUV provides any assistant role in differentiation of malignant vs. benign bone lesions. Methods: In this retrospective study we evaluated 137 patients with known or suspected bone metastases with different tumor entities (3 lung cancers, 28 breast cancers, 7 GI cancers, 5 medullary thyroid cancers, 79 prostate cancers and 15 miscellaneous) by F-18 Fluoride PET-CT. The final diagnosis of pathologic lesions was based on histopathologic results, follow-up or a consensus of morphologic and metabolic imaging modalities. Results: Overall 701 (354 malignant and 347 benign) lesions were evaluated. The morphological pattern of malignant lesions was correlated with CT (229 sclerotic, 43 mixed and 30 osteolytic lesions). Fifty five malignant lesions (confirmed by follow-up) showed no significant morphological changes on CT (probably due to bone marrow metastases or microsclerosis). The mean SUVmax was 21+-9 in benign lesions vs 48+-53 in malignant lesions. Additionally, a significant correlation was seen between tracer intensity by SUV and density of sclerotic lesions by HU (r=-18, p Conclusions: This study confirmed the value of F-18 Fluoride PET-CT in detection of malignant bone disease. It was not possible to differentiate benign from malignant lesions based on the intensity of F-18 Fluoride PET for SUV levels less than 57. However, an interesting finding was that in SUV levels greater than 57 all lesions were malignant.

1582 Objectives: F-18 Fluoride PET proved to be a highly sensitive method for detection of malignant bone disease. However, albeit it’s high sensitivity, there are some malignant bone lesions without F-18 Fluoride uptake. The aim of this study was to open a discussion for further clarification of F-18 Fluoride PET negative malignant sclerotic lesions. Methods: Fourteen patients with known or suspected bone metastases were evaluated retrospectively. Two patients underwent whole body F-18 Fluoride PET-CT for preoperative staging and 12 patients for follow-up evaluation (10 patients with prostate cancer, 2 patients breast cancer, 1 patient squamous cell cancer in the mandible and 1 patient with cancer of unknown origin). Results: Thirty one densely sclerotic lesions were detected on CT which were negative on F-18 Fluoride PET-CT. Mean density of sclerotic lesions by Hounsfield unit was 1221 +- 560. In retrospective monitoring, 5 lesions were positive in previous F-18 Fluoride PET studies. These F-18 Fluoride negative lesions remained negative in spite of diseases progression and new metastatic bone formations in the other sites of skeleton. Twenty seven F-18 Fluoride PET negative/ malignant sclerotic lesions (27/31) were detected in patients with previous therapy and 4 lesions (4/31) were seen in a patient without previous therapy. Conclusions: F-18 Fluoride PET could be also negative in the highly dense malignant sclerotic lesions. This may be due to therapy response (in post therapeutic evaluation) or apoptosis (in patients without previous therapy) or false negative F-18 Fluoride PET. Nevertheless, this issue needs further clarification.

The aim of this prospective study was to compare the potential value of 18F fluorocholine (FCH) and 18F fluoride positron emission tomography (PET)–CT scanning for the detection of bony metastases from prostate cancer.

1657 Objectives: Neuroendocrine tumors (NETs) are heterogeneous group of neoplasms characterized by their endocrine metabolism and histological pattern. 18F DOPA PET - CT was introduced as one of the most accurate functional method for evaluation of patients with neuroendocrine tumors. This study evaluates whether early dynamic acquisition gives more diagnostic information depending on different characteristic tumor pattern. Methods: Thirty six patients - 23 with NETs, 13 with medullary thyroid carcinoma (MTC) - underwent 18F DOPA PET - CT. Acquisition started 1 minute post intravenous injection of 18F DOPA (270 Mbq) with dynamic PET images from suspected region, defined by either conventional imaging techniques or clinical studies, during 8 minutes (1 min frames) followed by a static acquisition from thigh to base of skull. Imaging was performed on an integrated PET – CT system (Discovery LS®, GE Medical Systems, Milwaukee, USA), readings were interpreted by two experienced nuclear physicians and radiologists, using an Advantage Windows® workstation (GE) Results: Twenty - one patients had a negative scan in the suspected region where the dynamic scan was performed. In 6 patients (5 MTC, 1 NET) higher tracer intensity was visualized in foci detected in dynamic scan by means of SUVmax. One patient with NET had a significant pathological tracer uptake during the dynamic studies but surprisingly no tracer uptake in the static scan (10 min later). 5 patients (3 MTC, 2 NET) had increasing tracer intensity in static comparing with dynamic scans. In 3 patients with NETs no difference in tracer intensity was visualized in foci detected by two performance modalities. Conclusions: These preliminary results suggest that more investigations should be done to optimize imaging protocols by means of 18F DOPA PET - CT relating to different histological patterns of NETs. Furthermore only in few cases early dynamic images seems to provide the only one diagnostic certainty.