Fluoromethylcholine Research Articles

3,3-Dimethyl-1-Butanol and its Metabolite 3,3-Dimethylbutyrate Ameliorate Collagen-induced Arthritis Independent of Choline Trimethylamine Lyase Activity.

Conflicting data exist in rheumatoid arthritis and the collagen-induced arthritis (CIA) murine model of autoimmune arthritis regarding the role of bacterial carnitine and choline metabolism into the inflammatory product trimethylamine (TMA), which is oxidized in the liver to trimethylamine-N-oxide (TMAO). Using two published inhibitors of bacterial TMA lyase, 3,3-dimethyl-1-butanol (DMB) and fluoromethylcholine (FMC), we tested if TMA/TMAO were relevant to inflammation in the development of CIA. Surprisingly, DMB-treated mice demonstrated > 50% reduction in arthritis severity compared to FMC and vehicle-treated mice, but amelioration of disease was independent of TMA/TMAO production. Given the apparent contradiction that DMB did not inhibit TMA, we then investigated the mechanism of protection by DMB. After verifying that DMB acted independently of the intestinal microbiome, we traced the metabolism of DMB within the host and identified a novel host-derived metabolite of DMB, 3,3-dimethyl-1-butyric acid (DMBut). In vivo studies of mice treated with DMB or DMBut demonstrated efficacy of both molecules in significantly reducing disease and proinflammatory cytokines in CIA, while in vitro studies suggest these molecules may act by modulating secretion of proinflammatory cytokines from macrophages. Altogether, our study suggests that DMB and/or its metabolites are protective in CIA through direct immunomodulatory effects rather than inhibition of bacterial TMA lyases.

The roles of trimethylamine-N-oxide in atherosclerosis and its potential therapeutic aspect: A literature review.

Current research supports the evidence that the gut microbiome (GM), which consist of gut microbiota and their biologically active metabolites, is associated with atherosclerosis development. Trimethylamine-N-oxide (TMAO), a metabolite produced by the GM through trimethylamine (TMA) oxidation, significantly enhances the formation and vulnerability of atherosclerotic plaques. TMAO promotes inflammation and oxidative stress in endothelial cells, leading to vascular dysfunction and plaque formation. Dimethyl-1-butanol (DMB), iodomethylcholine (IMC) and fluoromethylcholine (FMC) have been recognized for their ability to reduce plasma TMAO by inhibiting trimethylamine lyase, a bacterial enzyme involved in the choline cleavage anaerobic process, thus reducing TMA formation. Conversely, indole-3-carbinol (I3C) and trigonelline inhibit TMA oxidation by inhibiting flavin-containing monooxygenase-3 (FMO3), resulting in reduced plasma TMAO. The combined use of inhibitors of choline trimethylamine lyase and flavin-containing monooxygenase-3 could provide novel therapeutic strategies for cardiovascular disease prevention by stabilizing existing atherosclerotic plaques. This review aims to present the current evidence of the roles of TMA/TMAO in atherosclerosis as well as its potential therapeutic prevention aspects.

Dual-Tracer PET-MRI-Derived Imaging Biomarkers for Prediction of Clinically Significant Prostate Cancer.

To investigate if imaging biomarkers derived from 3-Tesla dual-tracer [(18)F]fluoromethylcholine (FMC) and [68Ga]Ga-PSMAHBED-CC conjugate 11 (PSMA)-positron emission tomography can adequately predict clinically significant prostate cancer (csPC). We assessed 77 biopsy-proven PC patients who underwent 3T dual-tracer PET/mpMRI followed by radical prostatectomy (RP) between 2014 and 2017. We performed a retrospective lesion-based analysis of all cancer foci and compared it to whole-mount histopathology of the RP specimen. The primary aim was to investigate the pretherapeutic role of the imaging biomarkers FMC- and PSMA-maximum standardized uptake values (SUVmax) for the prediction of csPC and to compare it to the mpMRI-methods and PI-RADS score. Overall, we identified 104 cancer foci, 69 were clinically significant (66.3%) and 35 were clinically insignificant (33.7%). We found that the combined FMC+PSMA SUVmax were the only significant parameters (p < 0.001 and p = 0.049) for the prediction of csPC. ROC analysis showed an AUC for the prediction of csPC of 0.695 for PI-RADS scoring (95% CI 0.591 to 0.786), 0.792 for FMC SUVmax (95% CI 0.696 to 0.869), 0.852 for FMC+PSMA SUVmax (95% CI 0.764 to 0.917), and 0.852 for the multivariable CHAID model (95% CI 0.763 to 0.916). Comparing the AUCs, we found that FMC+PSMA SUVmax and the multivariable model were significantly more accurate for the prediction of csPC compared to PI-RADS scoring (p = 0.0123, p = 0.0253, respectively). Combined FMC+PSMA SUVmax seems to be a reliable parameter for the prediction of csPC and might overcome the limitations of PI-RADS scoring. Further prospective studies are necessary to confirm these promising preliminary results.

Thyroid and androgen receptor signaling are antagonized by μ-Crystallin in prostate cancer.

Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3′‐triiodo‐l‐thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ‐Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage‐specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3‐ and androgen‐mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.

18F]Fluorocholine PET/CT-guided stereotactic body radiotherapy in patients with recurrent oligometastatic prostate cancer

BackgroundIn the last years, functional imaging has given a significant contribution to the clinical decision-making of biochemically relapsed prostate cancer (PCa). Hereby, we present a prospective study aiming to validate the role of [18F]Fluoro-Methyl Choline ([18F]FMCH) PET/CT in the selection of PCa patients suitable for stereotactic body radiotherapy (SBRT).MethodsPatients with biochemical recurrence limited up to three lesions revealed by [18F]FMCH PET/CT were enrolled in the present study and treated with SBRT on all active lesions. Systemic therapy-free survival since the [18F]FMCH PET/CT was considered as the primary endpoint.ResultsForty-six patients were evaluated, and a total of 67 lesions were treated. After a median follow-up of 28.9 months, systemic therapy was started in 30 patients (65.2%) and median systemic therapy-free survival was 39.1 months (95% CI 6.5–68.6); 6, 12, and 24-month ratios were 93.5%, 73.9%, and 63.1%, respectively. At univariate Cox regression analysis, Delta PSA demonstrated an impact on systemic therapy-free survival (p < 0.001).ConclusionsBased on our findings, [18F]FMCH PET/CT can identify oligometastatic prostate cancer patients suitable for SBRT, resulting in a systemic therapy-free survival of 39.1 months.

Feasibility of Intraprostatic Prostate Cancer Imaging with FCH-PET/CT for Preoperative Planning of Image-Guided HDR Brachytherapy

To evaluate the feasibility of using [18F]-fluoromethylcholine (FCH) PET/CT imaging for dominant-intraprostatic lesion (DIL) localisation in HDR boost brachytherapy planning, and to perform biological dose escalation HDR boost on the imaged DIL.

Uptake of 18F-FET and 18F-FCH in Human Glioblastoma T98G Cell Line after Irradiation with Photons or Carbon Ions.

The differential diagnosis between recurrence of gliomas or brain metastases and this phenomenon is important in order to choose the best therapy and predict the prognosis but is still a big problem for physicians. The new emerging MRI, CT, and PET diagnostic modalities still lack sufficient accuracy. Radiolabeled choline and amino acids have been reported to show great tumor specificity. We studied the uptake kinetics of [18F]fluoromethyl-choline (FCH) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) by the T98G human glioblastoma cells from 20 to 120 min after irradiation either with photons at 2-10-20 Gy or with carbon ions at 2 Gy (at the National Centre for Oncological Hadrontherapy (CNAO), Pavia, Italy). We also evaluated the cell death and morphology changes induced by radiation treatment. Both FET and FCH are able to trace tumor behavior in terms of higher uptake for increased doses of radiation treatment, due to the upregulation of cells attempts to repair nonlethal damage. Our data suggest that both FCH and FET could be useful to analyze the metabolic pathways of glioblastoma cells before and after radiotherapy. Physicians will have to consider the different kinetics pathways of uptake concerning the two radiopharmaceuticals.

Automated Radiosynthesis and Bio-distribution of ［18F］Fluoromethyl Choline

Automated Radiosynthesis and Bio-distribution of ［18F］Fluoromethyl Choline

Impact of Organic Cation Transporters (OCT-SLC22A) on Differential Diagnosis of Intrahepatic Lesions.

Positron emission tomography (PET) using the cationic compound [18F]fluoromethylcholine (FCH) enhances the sensitivity for noninvasive classification of hepatic tumors due to peculiar patterns of accumulation. The underlying transporters are not known. We aim to identify the carriers mediating uptake of FCH in liver and to correlate their expression pattern with PET intrahepatic signal distribution to clarify the role of membrane transporters in FCH accumulation. FCH transport was characterized in cells overexpressing organic cation transporters (OCTs). OCT mRNA levels were determined in different types of hepatic lesions and correlated with FCH PET signal intensity. Additionally, OCT1 and OCT3 protein was analyzed in a subset of patients by Western blotting. HEK293 cells overexpressing OCT1, OCT2, or OCT3 showed higher intracellular levels of FCH in comparison with wild-type cells. mRNA levels of OCT1 paralleled protein levels and were significantly downregulated in hepatocellular carcinoma (HCC), hepatocellular adenoma (HCA), and, to a lesser extent, in focal nodular hyperplasia compared with matched nontumor tissues. In three patients with HCA, the FCH PET signal intensity was reduced relative to normal liver. This correlated with the simultaneous downregulation of OCT1 and OCT3 mRNA. In another patient with HCA, lesion and surrounding tissue did not show a difference in signal, coinciding with downregulation of OCT1 and upregulation of OCT3. Therefore, OCT1 is very likely a key transporter for the accumulation of FCH in the liver. The data support the hypothesis that the varying expression levels of OCT1 and OCT3 in focal liver lesions determine FCH PET signal intensity.

Adequate Diagnostic Performance of Combined [&amp;lt;sup&amp;gt;18&amp;lt;/sup&amp;gt;F]-Fluormethylcholine PET-CT with Diffusion-Weighted MRI in Primary Staging of High Risk Prostate Cancer

Introduction: [18F]-fluoro-methylcholine (FCH) PET/CT and MRI with diffusion-weighted MRI (DW-MRI) have insufficient performance in lymph node staging of primary prostate cancer by themselves, but the combination may perform better. We aim to prospectively determine the diagnostic performance of combined FCH PET and MRI for lymph node staging. Methods: This was a single site study of diagnostic accuracy in a well-defined group of 21 consecutive high-risk primary prostate cancer patients (>30% chance of lymph node metastases) in a large community hospital. We performed FCH PET/CT and MRI with DW-MRI prior to endoscopic extended pelvic lymph node dissection (EPLND). PET was fused and interpreted together with various MRI image sets (T1, T2, DWIBS) and was only scored positive when a lymph node seen on MRI coincided with increased focal FCH uptake on PET. Findings were compared with detailed histological evaluation, on a per-patient and per-region level. We calculated sensitivity, specificity, positive and negative predictive value of combined PET-MRI. Results: 14 out of 21 patients had metastatic lymph nodes with 37 out of 164 evaluable regions harboring metastases. On a per-patient analysis, PET-MRI had a sensitivity/specificity of 79/100% with a PPV/NPV of 100/77%. On a per-region analysis (n = 164) these figure were 65/99% and 96/91%, respectively. Conclusions: Combined DW-MRI and FCH PET/CT has a very high positive predictive value in high risk prostate cancer patients. If confirmed in larger series a positive combined scan may safely allow cancellation of surgical staging in selected patients, depending on local protocols in N1 M0 patients.

Spine metastases in prostate cancer: comparison of technetium‐99m‐MDP whole‐body bone scintigraphy, [18F]choline positron emission tomography(PET)/computed tomography (CT) and [18F]NaF PET/CT

To compare the diagnostic accuracy of the following imaging techniques in the detection of spine metastases, using magnetic resonance imaging (MRI) as a reference: whole-body bone scintigraphy (WBS) with technetium-99m-MDP, [18F]-sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) and [(18) F]-fluoromethylcholine (FCH) PET/CT. The study entry criteria were biopsy-proven prostate cancer, a positive WBS consistent with bone metastases, and no history of androgen deprivation. Within 30 days of informed consent, trial scans were performed in random order. Scans were interpreted blindly for the purpose of a lesion-based analysis. The primary target variable was bone lesion (malignant/benign) and the 'gold standard' was MRI. A total of 50 men were recruited between May 2009 and March 2012. Their mean age was 73 years, their median PSA level was 84 ng/mL, and the mean Gleason score of the tumours was 7.7. A total of 46 patients underwent all four scans, while four missed one PET/CT scan. A total of 526 bone lesions were found in the 50 men: 363 malignant and 163 non-malignant according to MRI. Sensitivity, specificity, positive and negative predictive values and accuracy were: WBS: 51, 82, 86, 43 and 61%; NaF-PET/CT: 93, 54, 82, 78 and 81%; and FCH-PET/CT: 85, 91, 95, 75 and 87%, respectively. We found that FCH-PET/CT and NaF-PET/CT were superior to WBS with regard to detection of prostate cancer bone metastases within the spine. The present results call into question the use of WBS as the method of choice in patients with hormone-naïve prostate cancer.

18F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node staging of prostate cancer: a prospective study of 210 patients

Study Type--Diagnostic (exploratory cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Staging of patients with prostate cancer is the cornerstone of treatment. However, after curative intended therapy a high portion of patients relapse with local and/or distant recurrence. Therefore, one may question whether surgical lymph node dissection (LND) is sufficiently reliable for staging of these patients. Several imaging methods for primary LN staging of patients with prostate cancer have been tested. Acceptable detection rates have not been achieved by CT or MRI or for that matter with PET/CT using the most common tracer fluoromethylcholine (FCH). Other more recent metabolic tracers like acetate and choline seem to be more sensitive for assessment of LNs in both primary staging and re-staging. However, previous studies were small. Therefore, we assessed the value of [(18) F]FCH PET/CT for primary LN staging in a prospective study of a larger sample and with a 'blinded' review. After a study period of 3 years and >200 included patients, we concluded that [(18) F]FCH PET/CT did not reach an optimal detection rate compared with LND, and, therefore, it cannot replace this procedure. However, we did detect several bone metastases with [(18) F]FCH PET/CT that the normal bone scans had missed, and this might be worth pursuing. • To assess the value of [(18) F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging of prostate cancer. • To evaluate if FCH PET/CT can replace LN dissection (LND) for LN staging of prostate cancer, as about one-third of patients with prostate cancer who receive intended curative therapy will have recurrence, one reason being undetected LN involvement. • From January 2008 to December 2010, 210 intermediate- or high-risk patients had a FCH PET/CT scan before regional LND. • After dissection, the result of histological examination of the LNs (gold standard) was compared with the result of FCH PET/CT obtained by 'blinded review'. • Sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of FCH PET/CT were measured for detection of LNe metastases. • Of the 210 patients, 76 (36.2%) were in the intermediate-risk group and 134 (63.8%) were in the high-risk group. A medium (range) of 5 (1-28) LNs were removed per patient. • Histological examination of removed LNs showed metastases in 41 patients. Sensitivity, specificity, PPV, and NPV of FCH PET/CT for patient-based LN staging were 73.2%, 87.6%, 58.8% and 93.1%, respectively. • Corresponding values for LN-based analyses were 56.2%, 94.0%, 40.2%, and 96.8%, respectively. • The mean diameter of the true positive LN metastases was significantly larger than that of the false negative LNs (10.3 vs 4.6 mm; P < 0.001). • In addition, FCH PET/CT detected a high focal bone uptake, consistent with bone metastases, in 18 patients, 12 of which had histologically benign LNs. • Due to a relatively low sensitivity and a correspondingly rather low PPV, FCH PET/CT is not ideal for primary LN staging in patients with prostate cancer. • However, FCH PET/CT does convey important additional information otherwise not recognised, especially for bone metastases.

Total Choline at 1H-MRS and [18F]-Fluoromethylcholine Uptake at PET

The use of in vivo imaging techniques for assessing choline metabolism to detect cancer is supported by studies showing increased choline kinase and transporter gene expression, transmembrane choline transport, and tissue choline metabolite concentration in a number of malignancies [1, 2]. Early clinical studies employing techniques for in vivo imaging of choline metabolism looked promising, with early PET studies demonstrating increased choline tracer uptake in a variety of tumors, and independently, studies employing proton magnetic resonance spectroscopy (1H-MRS) demonstrating increased tissue levels of choline metabolites in several malignancies [2–5]. However, the use of these two very different in vivo methods to study choline metabolism have raised questions as to how their measurements interrelate; and there have been instances where choline tracer uptake on PET fails to correlate well with the tissue measurements of choline provided by 1H-MRS [6]. To address these questions, Rommel et al., in their study titled “Rodent Rhabdomyosarcoma: Comparison Between Total Choline Concentration at 1H-MRS and [F]-fluoromethylcholine (FCH) Uptake at PET Using Accurate Methods for Collecting Data”, employed methods for achieving highly accurate spatial correspondence between small-animal PET and MRI to study the relationship between FCH uptake and spectroscopic measurement of tissue choline metabolites in a rhabdomyosarcoma animal model. Their study did not confirm a quantitative relationship between tumor FCH uptake and measures of choline concentration obtained with 1H-MRS in their experimental model. The authors offered several biological hypotheses to explain the lack of correlation between FCH uptake and choline metabolite concentration: one involving the presence of a negative feed-back mechanism of elevated levels of intracellular choline compounds on FCH uptake; another involving the rapid transport and incorporation of choline into membrane phosphatidylcholine (which is not detectable by 1H-MRS) to explain increases in FCH uptake without corresponding increases in total choline metabolite concentration on 1H-MRS. In addition to these biological hypotheses, the limited ability of in vivo 1H-MRS to discriminate specific choline metabolites may also be worth considering as a potential explanation for their observations. Specifically, the “choline peak” at 3.2 ppm that is often used for in vivo 1H-MRS studies is known to actually reflect a number of important choline metabolites [7]. Ex vivo and in vitro NMR can readily differentiate several of these metabolites bearing the choline moiety. They include free choline, phosphocholine (PC; at 3.23 ppm), and glycerophosphocholine (GPC; at 3.24 ppm) [8, 9]. However, due to their spectral proximity it has proven difficult to resolve these compounds in vivo [2]. PC is a predominant biosynthetic product whose concentrations in malignancy can increase as a result of choline kinase upregulation [1]. GPC, on the other hand, is primarily a product of phospholipase activation [10, 11]. In the study by Rommel et al., the inability to separate the spectral contributions of these biochemically distinct compounds should raise the question of whether FCH uptake is actually being compared to the net result of several anabolic and catabolic processes in the CDP-choline pathway. Such a situation could potentially explain the lack of correlation observed between total choline concentration and FCH uptake. Work by DeGrado et al. has suggested FCH to be a marker of biosynthetic PC metabolism with specificity for the transmembrane choline transporter and choline kinase [12, 13]. Consequently, the tissue concentration of PC, rather than total choline, may correlate best with FCH uptake. The relationship between PC and GPC metabolism under some tumor conditions has been studied. For example, activation of phospholipase can decrease PC and increase GPC levels in breast and prostate cancer cells, potentially leading to a less aggressive phenotype [11, 14]. Exposure to chemotherapeutic agents can also decrease tissue levels of PC while increasing the levels of GPC [15, 16]. These results suggest the possibility of assessing tumor therapeutic response through specific measurement of PC or GPC metabolism.We look forward to future studies comparing FCH PET to other methods for measuring PC metabolism in vivo.

Usefulness of Multimodal Investigations of the Choline Pathway

We feel very appropriate the present comments of Sandi Kwee and colleagues [1] on our experimental work comparing total choline concentration at H-MRS and choline uptake at [F]-fluoromethylcholine (FCH) [2]. As stated by Kwee et al., the so-called total choline peak (tCho) adds different metabolites having a common quaternary ammonium chemical group, prominently choline (Cho), phosphocholine (PC), and glycerophosphocholine [3]. Concentration and contribution of those different molecules can only be determined by high-resolution spectra at very high field strength from cellular extract in experimental settings. We fully agree with Kwee and colleagues when they hypothesize that tissue concentration of PC should have putatively better correlation to FCH uptake than tCho did. However, an a priori governing our work was to perform investigational experiments in a pre-clinical setting, therefore using an in vivo model and a clinical 3 T imager to allow easier translation to human patients’ cohorts in a further step. The major penalty we had then to assume using such system was its inability to separate the different sub-peaks of the ‘full’ tCho peak. However, we remain strongly convinced that the tCho peaks we obtained at 3 T significantly reflected tumor physiology as PC has been identified as the major choline component of H spectra [4, 5]. Thus far, the correlation between [F]-fluoromethylcholine uptake with tCho peak should remain an accurate indicator of what the correlation between FCH uptake and specific PC peak would have been. Furthermore, Al Saffar et al. observed that decrease in tCho and decrease in PC levels measured by P-MRS were similar in MDAMB-231 cells (human breast carcinoma) treated by an anticancer drug and thereby concluded that the decrease in tCho peak was mainly due to the drop in PC, as major component of the tCho peak [6]. Ultimately, we share the opinion that further experimental/pre-clinical studies comparing different choline imaging techniques in a synergistic way are mandatory to fully elucidate the complexity of the Kennedy pathway.

Rodent Rhabdomyosarcoma: Comparison Between Total Choline Concentration at H-MRS and [18F]-fluoromethylcholine Uptake at PET Using Accurate Methods for Collecting Data

To compare choline concentration/amount at proton magnetic resonance spectroscopy (H-MRS) and [18F]-fluoromethylcholine (FCH) uptake at positron emission tomography (PET) in a tumour animal model. Twenty-two rats bearing grafted syngenic rhabdomyosarcoma in both thighs were examined on a 3T MR system and on a small animal PET system. Total choline concentration was measured on proton MR spectra using a so-called 'best internal fitting' volume of interest. Choline uptake was expressed as mean and maximum standardized uptake value (SUV and SUVmax, respectively) and as the percent of injected dose (%ID) after tumour delineation on fused PET-MR images. Data sets were displayed on standard scatter plots. Thirty-six tumours were available for analysis. The area under the curve of the 3.2 ppm choline peak ranged from 69 to 476 (mean, 192) in arbitrary units. Mean SUV values ranged from 0.05 to 0.49 (mean, 0.19) and the %ID from 0.05 to 2.28 (mean, 0.54). Scatter plots failed to reveal quantitative relationship between choline concentration and uptake. Empirically data-driven cut-off lines applied to choline amount (choline concentration x tumour volume) versus choline uptake suggested a paradoxically negative relationship. Total choline concentration did not correlate with FCH uptake in a tumour experimental model. A negative feedback of high values of total choline amount on cellular FCH uptake seemed to be present.

Fluoromethylcholine PET in recurrent multifocal hepatoma

F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has variable efficacy in evaluating hepatocellular carcinoma. We present a case of a new oncologic imaging tracer fluoromethylcholine (FCH), which has visualized recurrent multifocal hepatoma in a patient with a poor FDG avid hepatic tumour. The lesions demonstrated on FCH PET correlated well with the findings on CT hepatic angiography.

18F]fluorocholine PET/CT imaging for the detection of recurrent prostate cancer at PSA relapse: experience in 100 consecutive patients

We evaluated the potential of PET/CT and [(18)F]fluoromethylcholine (FCH) in the assessment of suspected recurrence of prostate cancer after treatment. One hundred consecutive prostate cancer patients with a persistent increase in serum PSA (>0.1 ng/ml) after radical prostatectomy (58 cases), radiotherapy (21 cases) or hormonal therapy alone (21 cases) were investigated. After injection of 3.7-4.07 MBq/kg of FCH, both early (at <15 min) and delayed (at >60 min) PET/CT scans were performed in 43 patients, delayed PET/CT scans in 53 patients and early PET/CT scans in four patients. Of the 100 patients, 54 (PSA 0.22-511.79 ng/ml) showed positive FCH PET/CT scans. Thirty-seven patients had bone and/or abdominal lymph node uptake, while 17 showed pelvic activity. Malignant disease was confirmed in all but one. Delayed SUV(max) of bone metastases was significantly higher (p<0.0001 by paired t test) than that measured at <15 min, whereas no differences were observed between early and delayed SUVs of malignant lymph nodes or pelvic disease. Forty-six patients (PSA 0.12-14.3 ng/ml) showed negative FCH PET/CT scans. Of the negative PET/CT scans, 89% were obtained in patients with serum PSA <4 ng/ml and 87% in patients with a Gleason score <8. In none of these cases could recurrent tumour be proven clinically during a follow-up of 6 months. FCH PET/CT is not likely to have a significant impact on the care of prostate cancer patients with biochemical recurrence until PSA increases to above 4 ng/ml. However, in selected patients, FCH PET/CT helps to exclude distant metastases when salvage local treatment is intended.