Captive solvent [11C]acetate synthesis in GMP conditions.

Reliable procedure for the production of 1-[(11)C]acetate in GMP conditions was developed based on a combination of the captive-solvent Grignard reaction conducted in the sterile catheter followed by the convenient solid-phase extraction purification on a series of ion-exchange cartridges. The described procedure proved to be reliable in more than 30 patient productions. The process provides stable radiochemical yields (65% EOB) of sodium acetate (1-[(11)C]) of the Ph.Eur. quality (radiochemical purity better than 95%) in a short time (5 min).

Preparation of [11C] radioligands with high specific radioactivity on a commercial PET tracer synthesizer.

High specific radioactivity is required for receptor studies with PET. Hereby we wish to report our experience using Nuclear Interface PET Tracer Synthesizer for preparation of Carbon-11 radioligands and module's modifications, which allowed to achieve high specific radioactivity.

Automation of [11C]acyl chloride syntheses using commercially available 11C-modules.

In implementing published procedures for the incorporation of [11C]carbon dioxide on the immobilized Grignard reagents for the radiosynthesis of [11C]acyl chlorides, several modifications on a commercial PET tracer synthesizer module for 11C-methylations were made to obtain reliable and reproducible production processes for routine clinical applications. High yields of [carbonyl-11C]WAY-100635 and [11C]zofenoprilat were obtained via 11C-carboxylation using [carbonyl-11C]cyclohexanecarbonyl chloride and 2-methyl-[l-11C]acryloyl chloride prepared with the modified module.

Evaluation of the sensitivity and specificity of (11)C-metomidate positron emission tomography (PET)-CT for lateralizing aldosterone secretion by Conn's adenomas.

CONTEXT: Identification of unilateral aldosterone-producing (Conn's) adenomas has traditionally required lateralization by the invasive and technically difficult procedure of adrenal vein sampling (AVS). (11)C-metomidate, a potent inhibitor of adrenal steroidogenic enzymes, is a positron emission tomography (PET) radiotracer that is selectively accumulated by Conn's adenomas. OBJECTIVE: The objective of the study was to compare the sensitivity and specificity of (11)C-metomidate PET-computed tomography (CT) against the current gold standard of AVS. DESIGN: The design of the study was within-patient comparison of diagnostic techniques. SETTING: The study was conducted at a single center-university teaching hospital. PATIENTS: Thirty-nine patients with primary hyperaldosteronism (PHA) and five with nonfunctioning adenomas (incidentalomas) participated in the study. INTERVENTION(S): The first six PHA patients were studied on three occasions to determine whether steroid pretreatment reduced (11)C-metomidate uptake by normal adrenal. Subsequent patients received dexamethasone for 3 d prior to injection of (11)C-metomidate 150-500 MBq. MAIN OUTCOME MEASURE(S): Maximum standardized uptake values (SUV(max)) over regions of interest determined from 35-45 min after injection were measured. RESULTS: Dexamethasone increased tumor to normal adrenal SUV(max) ratio by 25.6 ± 5.0% (P < 0.01). PET-CT visualized subcentimeter adenomas and distinguished hot from cold adenomas within a gland. In 25 patients with PHA and AVS lateralization to the side of an adenoma, SUV(max) over tumor (mean ± sem) of 21.7 ± 1.6 was greater than over normal adrenal, 13.8 ± 0.6 (P = 0.00003); this difference was absent in 10 patients without lateralization on AVS (P = 0.28) and in four of five incidentalomas. On receiver-operator characteristics analysis, an SUV(max) ratio of 1.25:1 provided a specificity of 87% [95% confidence interval (69, 104)] and sensitivity of 76% (59, 93); in tumors with SUV(max) greater than 17, the specificity rose to 100%. CONCLUSIONS: (11)C-metomidate PET-CT is a sensitive and specific noninvasive alternative to AVS in the management of PHA.

PET imaging with 11C-acetate in prostate cancer: a biochemical, radiochemical and clinical perspective.

PURPOSE: In the present study, the potential clinical role of 11C-acetate PET mainly in the differential diagnosis, in the staging and in the follow-up of prostate cancer patients is reported. METHODS: Each of the above points has been accurately investigated by studying the specific biochemical and radiobiochemical behaviour of this positron emitter compound. RESULTS AND CONCLUSION: The imaging quality of 11C-acetate PET and its unique mechanisms of cellular uptake, make such radiotracer a powerful tool in evaluating all the steps of the prostatic cancer.

18F-choline and/or 11C-acetate positron emission tomography: detection of residual or progressive subclinical disease at very low prostate-specific antigen values (<1 ng/mL) after radical prostatectomy.

OBJECTIVES: To assess the value of positron emission tomography (PET)/computed tomography (CT) with either (18)F-choline and/or (11)C-acetate, of residual or recurrent tumour after radical prostatectomy (RP) in patients with a prostate-specific antigen (PSA) level of <1 ng/mL and referred for adjuvant or salvage radiotherapy. PATIENTS AND METHODS: In all, 22 PET/CT studies were performed, 11 with (18)F-choline (group A) and 11 with (11)C-acetate (group B), in 20 consecutive patients (two undergoing PET/CT scans with both tracers). The median (range) PSA level before PET/CT was 0.33 (0.08-0.76) ng/mL. Endorectal-coil magnetic resonance imaging (MRI) was used in 18 patients. Nineteen patients were eligible for evaluation of biochemical response after salvage radiotherapy. RESULTS: There was abnormal local tracer uptake in five and six patients in group A and B, respectively. Except for a single positive obturator lymph node, there was no other site of metastasis. In the two patients evaluated with both tracers there was no pathological uptake. Endorectal MRI was locally positive in 15 of 18 patients; 12 of 19 responded with a marked decrease in PSA level (half or more from baseline) 6 months after salvage radiotherapy. CONCLUSIONS: Although (18)F-choline and (11)C-acetate PET/CT studies succeeded in detecting local residual or recurrent disease in about half the patients with PSA levels of <1 ng/mL after RP, these studies cannot yet be recommended as a standard diagnostic tool for early relapse or suspicion of subclinical minimally persistent disease after surgery. Endorectal MRI might be more helpful, especially in patients with a low likelihood of distant metastases. Nevertheless, further research with (18)F-choline and/or (11)C-acetate PET with optimal spatial resolution might be needed for patients with a high risk of distant relapse after RP even at low PSA values.

(11)C-acetate PET in the early evaluation of prostate cancer recurrence.

PURPOSE: The first aim of the study was to investigate the diagnostic potential of (11)C-acetate PET in the early detection of prostate cancer recurrence. A second aim was the evaluation of early and late PET in this context. METHODS: The study population comprised 32 prostate cancer patients with early evidence of relapse after initial radiotherapy (group A) or radical surgery (group B). The median PSA of group A (n=17) patients was 6 ng/ml (range 2.6-30.2) while that of group B (n=15) was 0.4 ng/ml (range 0.08-4.8). Pelvic-abdominal-thoracic PET was started 2 min after injection of (11)C-acetate and evaluated after fusion with CT. RESULTS: Group A: Taking a SUV(max)> or =2 as the cut-off, PET showed local recurrences in 14/17 patients and two equivocal results. Distant disease was observed in six patients and an equivocal result was obtained in one. Endorectal MRI was positive in 12/12 patients. Biopsy confirmed local recurrence in six of six (100%) patients. PET was positive in five of the six patients with biopsy-proven recurrences, the result in the remaining patient being equivocal. Group B: Among the 15 patients, visual interpretation was positive for local recurrences in five patients and equivocal in four. One obturator lymph node was positive. Endorectal MRI was positive in 11/15 patients and equivocal in two. Positional correlation of positive/equivocal results on PET and endorectal MRI was observed in seven of nine patients. PSA decreased significantly after salvage radiotherapy in 8/14 patients, providing strong evidence for local recurrence. PET of the eight patients responding to RT was positive in three and equivocal in two. CONCLUSION: (11)C-acetate PET was found to be valuable in the early evaluation of prostate cancer relapse. Optimising scanning time and use of modern PET-CT equipment might allow further improvement.