Estimation of absorbed dose for 2-[F-18]fluoro-2-deoxy-d- glucose using whole-body positron emission tomography and magnetic resonance imaging

The purpose of this study was to measure the cumulated activity and absorbed dose in organs after intravenous administration of 2-[F-18]fluoro-2-deoxy-d-glucose (¹⁸F-FDG) using whole-body positron emission tomography (PET) and magnetic resonance imaging (MRI). Whole-body dynamic emission scans for ¹⁸F-FDG were performed in six normal volunteers after transmission scans. The total activity of a source organ was obtained from the activity concentration of the organ measured by whole-body PET and the volume of that organ measured by whole-body T1-weighted MRI. The cumulated activity of each source organ was calculated from the time-activity curve. Absorbed doses to the individuals were estimated by the MIRD (medical internal radiation dosimetry) method using S-values adjusted to the individuals. Another calculation of cumulated activities and absorbed doses was performed using the organ volumes from the MIRD phantom and the ”Japanese reference man” to investigate the discrepancy of actual individual results against the phantom results. The cumulated activities of 18 source organs were calculated, and absorbed doses of 27 target organs estimated. Among the target organs, bladder wall, brain and kidney received the highest doses for the above three sets of organ volumes. Using measured individual organ volumes, the average absorbed doses for those organs were found to be 3.1×10^–1, 3.7×10^–2 and 2.8×10^–2 mGy/MBq, respectively. The mean effective doses in this study for individuals of average body weight (64.5 kg) and the MIRD phantom of 70 kg were the same, i.e. 2.9×10^–2 mSv/MBq, while for the Japanese reference man of 60 kg the effective dose was 2.1×10^–2 mSv/MBq. The results for measured organ volumes derived from MRI were comparable to those obtained for organ volumes from the MIRD phantom. Although this study considered ¹⁸F-FDG, combined use of whole-body PET and MRI might be quite effective for improving the accuracy of estimations of the cumulated activity and absorbed dose of positron-labelled radiopharmaceuticals. Received 23 October 1997 and in revised form 31 January 1998     

Evaluation of the treatment response of lung cancer with positron emission tomography and l-[methyl-11C]methionine: a preliminary study

We carried out a study to evaluate treatment response and residual mass in lung cancer with positron emission tomography (PET), using l-[methyl-¹¹C]methionine (MET). MET tumour uptake and tumour volume measured by computed tomography (CT) before and within 2 weeks after radiotherapy or chemoradiotherapy were compared in 43 studies of 21 patients. Ten patients with local control (no recurrence) of tumour showed a larger decrease in MET uptake (65.2%±12.2%) than in tumour volume (50.8%±9.6%, P<0.01). Five patients with early recurrence (from 1 to 4 months) showed smaller decreases in both MET uptake (22.2%±13.5%) and tumour volume (28.6%±20.0%) than those in the no-recurrence group (P<0.01). Four patients with late recurrence (after 11 months or more) showed a similar decrease to the no-recurrence group in MET uptake (72.8%±14.8%) but little change in tumour volume (18.5%±19.0%), the latter result corresponding to that in the early-recurrence group. Using tumour volume only, the no-recurrence group was differentiated from both the early- and the late-recurrence group (P < 0.01), but the early-recurrence group was not differentiated from the late-recurrence group. Using the MET uptake data, the early-recurrence group was clearly distinguished from the late-recurrence group (P<0.01), but the late-recurrence group was indistinguishable from the no-recurrence group. CT was useful in distinguishing the no-recurrence group from the groups in which there was ultimate recurrence, whether early or late. When a residual mass is seen on CT, PET seems to be helpful in evaluating tumour viability. Correspondence to: K. Kubota     

O-(2-[18F]Fluoroethyl)-l-tyrosine and l-[methyl-11C]methionine uptake in brain tumours: initial results of a comparative study

O-(2-[¹⁸F]Fluoroethyl)-l-tyrosine (FET) is a recently described amino acid analogue that has shown high accumulation in animal tumours. The aim of this study was to compare the uptake of FET with that of l-[methyl-¹¹C]methionine (MET) in patients with suspected primary or recurrent intracerebral tumours. Sixteen consecutive patients with intracerebral lesions were studied on the same day by positron emission tomography (PET) using MET and FET. Uptake of FET and MET was quantified by standardized uptake values. Tracer kinetics for normal brain and intracerebral lesions were compared. On the basis of the MET-PET studies, viable tumour tissue was found in 13 patients. All tumours showed rapid uptake of FET and were visualized with high contrast. Mean uptake of FET for normal grey matter, white matter and tumour tissue was 1.1±0.2, 0.8±0.2 and 2.7±0.8 SUV, respectively. In all three tissues, uptake of MET was slightly higher (1.4±0.2, 0.9±0.1 and 3.3±1.0 SUV; P<0.01). However, contrast between tumour and normal tissues was not significantly different between MET and FET. Uptake of FET in non-neoplastic lesions (1.0±0.1 SUV) was significantly lower than in tumour tissue (P=0.007). For all lesions there was a close correlation (r=0.98) between MET and FET uptake. In conclusion, in PET studies of human brain tumours, the uptake and image contrast of FET appear to be very similar to those of MET. The specificity of FET for tumour tissue is promising but has to be addressed in a larger series of patients with non-neoplastic lesions. Received 24 October 1999 and in revised form 19 January 2000     

Crossed cerebellar diaschisis: a positron emission tomography study withl-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-d-glucose

OBJECTIVE: Crossed cerebellar diaschisis (CCD) is defined as a depression of blood flow and oxidative metabolism of glucose in the cerebellum contralateral to a supratentorial brain lesion, as detected with positron emission tomography (PET) and single photon emission computed tomography. We examined whether L-[methyl-11C]methionine (MET) uptake is affected in CCD. METHODS: In 12 patients with a unilateral supratentorial brain tumor, we evaluated the uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and MET in the cerebellar hemispheres by means of PET. Asymmetry index (AI) was defined as a difference in the average count between the ipsilateral and contralateral cerebellar hemispheres divided by the average count in both cerebellar hemispheres. Patients with AI of FDG PET more than 0.1 and those with AI equal to 0.1 or less than 0.1 were classified as CCD-positive and CCD-negative, respectively. RESULTS: Six patients were CCD-positive and others were CCD-negative in the FDG PET study. Between CCD-positive and CCD-negative patients, mean AI of MET was not significantly different (0.017 +/- 0.023 and 0.014 +/- 0.039, respectively). CONCLUSIONS: Different from glucose metabolism, cerebellar MET uptake was not affected in CCD. The present study may indicate that cerebellar MET uptake is independent of suppression of cerebellar neuronal activity.     

Changes in myocardial oxidative metabolism after biventricular pacing as evaluated by [11C]acetate positron emission tomography

A 70-year-old woman with dilated cardiomyopathy and recurrent severe heart failure was admitted for biventricular pacing (BVP), which was recently reported to have clinical efficacy for severe heart failure with intraventricular conduction delay. An electrocardiogram showed complete left bundle branch block, and the QRS interval was markedly prolonged at 195 msec. Echocardiogram showed marked dilatation, diffuse hypokinesis and dyssynchrony of the left ventricle, and grade III mitral valve regurgitation. The patient underwent implantation of an atriobiventricular pacemaker and three pacing leads transvenously. The QRS interval shortened to 165 msec immediately after the BVP therapy, and improvements in echocardiographic parameters were seen at 5 months after BVP therapy. Myocardial oxidative metabolism was assessed by the monoexponential clearance rate of [¹¹C]acetate (Kmono) as measured by positron emission tomography (PET), and myocardial efficiency was assessed by the work metabolic index (WMI) at 1 and 5 months after the BVP therapy. The PET images obtained 5 months after BVP therapy showed a decrease in the clearance of [¹¹C]acetate compared with that obtained 1 month after BVP therapy. The Kmono of the whole left ventricle decreased from 0.051 at 1 month to 0.038 min⁻¹ at 5 months after BVP therapy, and that of the septum, anterior wall, lateral wall and posterior wall also decreased. The WMI increased from 4.2×10⁶ to 6.8×10⁶ mmHg·ml/m². These results suggest that BVP improved left ventricular function without increasing myocardial oxidative metabolism, resulting in improved myocardial efficiency, and that BVP may improve the long-term prognosis of heart failure patients with ventricular dyssynchrony. [¹¹C]acetate PET is a useful method of evaluating global and regional myocardial oxidative metabolism in patients who have undergone BVP therapy.     

Dynamic study of methionine uptake in glioma using positron emission tomography

In order to evaluate the methionine uptake of a glioma with positron emission tomography (PET), the kinetics of carbon-11 methionine was investigated in 11 patients by measuring the free ¹¹C-methionine in plasma as an input function following intravenous administration. When the mean clearance curve of free ¹¹C-methionine in plasma instead of individual ¹¹C-methionine clearance curves was used, mean differences in uptake rate and distribution volume were 4.0% and 4.6% respectively. By applying the mean clearance curve of free ¹¹C-methionine in 18 glioma patients, significant differences in ¹¹C-methionine uptake rate and distribution volume were found according to pathological grading. For the accurate evaluation of the metabolism of ¹¹C-methionine, it is therefore preferable that the actual level of free ¹¹C-methionine in the plasma be measured, especially for the follow-up of individual cases. The study also demonstrated that the mean clearance curve of ¹¹C-methionine in plasma might be employed as an input curve for calculating the uptake rate and distribution volume with small errors. Offprint requests to: K. Sato     

A clinical evaluation of the quantitative accuracy of simultaneous emission/transmission scanning in whole-body positron emission tomography

We present a clinical evaluation of the quantitative bias which is introduced during simultaneous emission/transmission (SET) acquisition for the application of whole-body positron emission tomography (PET) with fluorine-18 2-fluoro-2-deoxy-d-glucose. The quantitative accuracy of the SET technique was assessed by means of a clinical study involving 28 patients and a realistic phantom experiment. In the clinical study, SET overestimated the activity concentration in the tumours by a factor of approximately 1.10, but in the phantom study, where the tumours were smaller, the bias was found to increase to a value of 1.39. The bias in the soft tissue regions of the patient studies varied between 1.03 and 1.36, and close agreement was observed with the corresponding phantom results. The extent of the bias increased as the local activity concentration decreased and we attribute the effect to scattered photons from the transmission source which are detected in the emission window during SET. Received 23 September and in revised form 11 December 1997     

Whole-body positron emission tomography using fluorodeoxyglucose for staging of lymphoma: effectiveness and comparison with computed tomography

The purpose of this study was to evaluate whole-body positron emission tomography (WB-PET) as a staging modality in Hodgkin’s disease (HD) and non-Hodgkin lymphoma (NHL) and to compare it with computed tomography (CT) in a retrospective study. Seventy-one WB-PET studies using fluorodeoxyglucose (FDG) and 49 CT examinations were performed in 19 women and 31 men. Transaxial images were acquired and reformatted coronally and sagittally in PET. CT sections were obtained from the skull base to the pelvic floor. The written reports of the imaging data were compared with a reference standard constructed on the basis of all the data on the individual patients, including clinical follow-up of at least 6 months. The sensitivity and specificity of PET were, respectively, 86% and 96% for HD (n=53), and 89% and 100% for NHL (n=18). For CT sensitivity and specificity were 81% and 41% for HD (n=33) and 86% and 67% for NHL (n=16). Differences between PET and CT sensitivities were not significant, while in HD there was a significant difference in the specificity of PET and CT examinations, mainly because CT was unable to distinguish between active or recurrent disease and residual scar tissue after therapy. FDG tumour uptake was found in high- as well as low-grade NHL patients. In conclusion, PET appears to be highly sensitive and specific for staging of lymphoma. It is at least as sensitive as CT, and more specific, particularly in patients undergoing restaging, where a well-recognized diagnostic dilemma in CT is the presence of a post-therapeutic residual mass. Received 5 January and in revised form 10 March 1998     

Development and evaluation of muscarinic cholinergic receptor ligands N-[11C]ethyl-4-piperidyl benzilate and N-[11C]propyl-4-piperidyl benzilate: a PET study in comparison with N-[11C]methyl-4-piperidyl benzilate in the conscious monkey brain

The muscarinic cholinergic receptor ligands N-[¹¹C]ethyl-4-piperidyl benzilate (4-EPB) and N-[¹¹C]propyl-4-piperidyl benzilate (4-PPB) were developed and evaluated in comparison with N-[¹¹C]methyl-4-piperidyl benzilate (4-MPB) in the conscious monkey brain using positron emission tomography (PET). Time-activity curves of [¹¹C]4-EPB, unlike [¹¹C]4-MPB, showed peaks within 91 min in regions rich in muscarinic receptors. [¹¹C]4-PPB showed no specific binding even in the regions rich in these receptors. These observation demonstrated that increases in [¹¹C]alkyl chain length could alter the kinetic properties of receptor ligands for PET.     

Preclinical studies on [11C]MPDX for mapping adenosine A1 receptors by positron emission tomography

In previous in vivo studies with mice, rats and cats, we have demonstrated that [11C]MPDX ([1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine) is a potential radioligand for mapping adenosine A1 receptors of the brain by positron emission tomography (PET). In the present study, we performed a preclinical study. The radiation absorbed-dose by [11C]MPDX in humans estimated from the tissue distribution in mice was low enough for clinical use, and the acute toxicity and mutagenicity of MPDX were not found. The monkey brain was clearly visualized by PET with [11C]MPDX. We have concluded that [11C]MPDX is suitable for mapping adenosine A1 receptors in the human brain by PET.     

Use of carbon-11 methionine positron emission tomography to assess malignancy grade and predict survival in patients with lymphomas

The aim of this study was to investigate whether uptake of carbon-11 methionine (MET) is associated with histological grade of malignancy and survival in patients with newly diagnosed or recurrent lymphoma. Thirty-two patients with histologically confirmed lymphoma participated in the study. Twenty-six (81%) were studied before any therapy and six before treatment for recurrent disease. Twenty-eight patients had non-Hodgkin’s lymphoma and four had Hodgkin’s disease. An ECAT 931/08-12 positron emission tomography (PET) scanner was used for PET imaging. After the transmission scan, a median dose of 293 MBq of MET was injected intravenously and dynamic images were acquired for 40 min. The uptake of MET in tumour was measured as the standardized uptake value (SUV) and influx constant (K _i). The SUV formula was also adjusted to the predicted value of lean body mass (SUV_lean) and body surface area (SUV_BSA). The PET results were correlated with the clinical follow-up data. The median SUV in 32 malignant lesions was 6.6 (range, 1.9–12.4) and the median K _i was 0.116 min⁻¹ (range, 0.025–0.201, n=23). The median SUV was 7.0 (range, 5.4–12.4, n=9) in high, 6.2 (range, 1.9–10.4, n=11) in intermediate and 5.7 (range, 3.8–8.3, n=8) in low grade lymphomas. One intermediate grade lymphoma of the skin was visually negative (SUV 1.9). In Hodgkin’s disease the median SUV was 7.0 (range, 3.2–7.9, n=4). The median K _i value was 0.162 min⁻¹ (range, 0.147–0.197, n=7) in high, 0.099 (range, 0.025–0.152, n=10) in intermediate, and 0.078 (range, 0.056–0.152, n=4) in low grade lymphomas and 0.149 (range, 0.096–0.201, n=2) in Hodgkin’s disease. The difference between high and other grade non-Hodgkin’s lymphomas was significant when using K _i (P<0.001), but not with SUV, SUV_lean or SUV_BSA. The final outcome of the patients was not related to MET uptake. Lymphomas with a high K _i value tended to have a high S-phase fraction (r ²=0.46, P=0.043). It is concluded that MET PET is highly sensitive for the detection of untreated and recurrent lymphomas. Differentation of high grade lymphomas from lower malignancy grades seems to be possible if graphical analysis is applied to calculate K _i for MET. However, prediction of survival is not possible with MET PET. Received 5 March and in revised form 25 April 1998     

Metabolic fate of L-[methyl-11C]methionine in human plasma

The metabolites of L-[methyl-¹¹C]methionine in the plasma of 8 patients with tumor were measured for 60 min after injection. In the plasma, after a rapid clearance, the total radioactivity remained constant, and protein-bound radioactivity increased rapidly. Non protein metabolites detected by HPLC as at least two components besides methionine, increased with time. Significant individual variations for the metabolism were observed. AT 60 min after injection, 36.5% (range: 16%–72%) and 45.3% (range: 13%–74%) of the ¹¹C was measured as methionine and labeled proteins, respectively.     

PET studies with l-[1-11C]tyrosine,l-[methyl-11C]methionine and 18F-fluorodeoxyglucose in prolactinomas in relation to bromocryptine treatment

Aspects of metabolism in prolactinomas were investigated by positron emission tomography using l-[1-¹¹C]tyrosine, l-[methyl-¹¹C]methionine and ¹⁸F-fluorodeoxyglucose (¹⁸FDG). Using l-[1-¹¹C]tyrosine, four patients were monitored prior to and 18 h after an injection of 50 mg bromocryptine. At 18 h after bromocryptine intervention, l-[1-¹¹C]tyrosine uptake into tumour was reduced with 28% (P<0.07). A correlation analysis of the bromocryptine-induced decrease in l-[1-¹¹C]tyrosine uptake and the reduction of serum prolactin levels indicated that the action of bromocryptine on prolactin synthesis and prolactin release is not coupled. In the untreated situation, the four patients were investigated with ¹⁸FDG as well, but the prolactinomas could not be visualized. Three untreated patients were studied with l-[methyl-¹¹C]methionine. The tumour-imaging potential of l-[methyl-¹¹C]methionine and l-[1-¹¹C]tyrosine appeared to be nearly equivalent for prolactinomas. Unlike prolactinoma tissue, the salivary glands showed a pronounced preference for l-[1-¹¹C]tyrosine as compared to l-[methyl-¹¹C]methionine. l-[1-¹¹C]tyrosine is a valuable tool to obtain information on the metabolism and treatment of prolactinomas.     

Evaluation of recurrent gastric malignancy with [F-18]-FDG positron emission tomography

AIM: We retrospectively assessed the use of [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) in the evaluation of recurrent disease in patients with history of gastric malignancy. MATERIALS AND METHODS: Eighteen patients were referred for FDG PET for evaluation of recurrent gastric cancer. Prior treatments included total (n = 4) or partial gastrectomy (n = 14) followed by chemotherapy alone (n = 7) or combined chemoradiation therapy (n = 2). The interval between the most recent treatment and PET ranged from 3 months to 2 years. Correlative diagnostic data were available in 16 patients and were all obtained within 3 months of the PET study. Validation was by clinical or imaging follow-up (2-45 months) in 16 patients and histology in two patients. RESULTS: PET was concordant with computed tomography (CT) in 12 patients (5 TP, 6 TN, 1 FN). In one patient with negative imaging studies, an incidental finding of left obstructive uropathy was determined to be due to metastatic ureteral stricture. Discordant imaging findings were present in four patients (22% of total). PET-detected diffuse metastatic lesions in three of these patients with rising serum tumour markers while other imaging studies were negative. Additional chemotherapy was initiated in these three patients (17% of total) based on PET localization of disease. PET and a gastric anastomosis biopsy were negative in another patient with positive CT. The remaining two patients without correlative imaging studies died shortly after positive PET studies with presumed recurrent cancer. CONCLUSION: FDG PET may be useful in the evaluation of recurrent gastric cancer, and can localize the disease when CT is non-diagnostic. Imaging evaluation with PET may also impact on the clinical management of patients with recurrent gastric cancer.     

Imaging of adenosine A<Subscript>1</Subscript> receptors in the human brain by positron emission tomography with [<Superscript>11</Superscript>C]MPDX

We report the first clinical PET study using [1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine ([11C]MPDX) for imaging adenosine A1 receptors in the human brain. The binding of [11C]MPDX evaluated quantitatively as the distribution volume by a graphical analysis was high in the striatum and thalamus, and low in the cerebellum. The distribution pattern of [11C]MPDX was coincident with that of adenosine A1 receptors in vitro reported previously, and was different from those of blood flow and [18F]FDG. The [11C]MPDX PET has the potential for mapping adenosine A1 receptors in the human brain.     

Evaluation of treatment effects in brain abscess with positron emission tomography: Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine

Positron emission tomography (PET) imaging is in common use preoperatively to clinically evaluate patients who present with central nervous system mass lesions. The usefulness of PET is also recognized as a method to detect intracranial tumorous lesions. A number of papers reportthat some inflammatory processes also showed the uptake of Fluorine-18-Fluorodeoxyglucose (FDG) and Carbon-11-Methionine (Met) tracers. We performed two PET studies before and after treatment in 4 patients with brain abscess. PET showed the uptake of both tracers to thebrain abscess before treatment. The area showing an increased uptake of Met corresponded closely to the enhanced area on both CT and MR images. FDG-PET visually showed an uptake of FDG in a small area corresponding to an enhanced lesion within the CT and MR images. After treatment the area of lesions became small on enhancement CT or MRI and both PET studies showed reduced lesion and decreased uptake. The mechanism of Met uptake in the inflammatory area may be related to the higher metabolic rate and the active transport of amino acids as well as disruption of the blood brain barrier. Furthermore, it appears that the mechanism of FDG uptake is also related to a higher metabolic rate and, in addition, is related to the increased density of inflammatory cells. PET studies, more directly, reflect the degree of inflammatory response in brain abscess than enhancement CT or MRI. Therefore, PET is useful in detecting the inflammatory lesion and assessing the clinical effects of antibiotics treatment on brain abscesses.     

2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography initial staging impacts on survival in Hodgkin lymphoma

AIM: To assess the prognostic value and risk classification improvement of metabolic staging (MS) with Initial 2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography (FDG-PET) in initial staging of Hodgkin’s Lymphoma (HL) patients to predict 5 years overall survival (5y-OS) and event free survival (EFS).METHODS: A total of 275 patients were included in this retrospective study, 155 patients were staged with conventional anatomical staging (AS), and 120 also submitted to MS (FDG-PET). Prognostic analysis compared 5y-OS and 5y-EFS of patients staged with AS and MS. Risk-adjusted models incorporated clinical risk factors, computed tomography and FDG-PET staging.RESULTS: During the follow up of 267 evaluated patients, 220 (122 AS and 98 MS) achieved complete remission after first-line therapy (median follow-up: 70 ± 29 mo), treatment failure occurred in 79 patients and 34 died. The 5y-EFS for early vs advanced disease in AS patients was 79.3% and 66.7%, and 85.6% and 53.6% in MS patients, respectively (P < 0.01). The 5y-OS for early and advanced disease with AS was 91.3% and 81.5%, and 97.5% and 80.7% for patients staged with MS, respectively. Cox proportional hazards analysis demonstrated that FDG-PET added significant prognostic information and improved risk prediction (P = 0.02).CONCLUSION: Initial staging FDG-PET could be used as an accurate and independent predictor of OS and EFS in HL, with impact in 5y-EFS and OS.     

Protein synthesis rate measured with l-[1-11C]tyrosine positron emission tomography correlates with mitotic activity and MIB-1 antibody-detected proliferation in human soft tissue sarcomas

Protein synthesis rate (PSR) can be assessed in vivo using positron emission tomography with l-[1-¹¹C]tyrosine (TYR-PET). Biological activity of soft tissue sarcomas (STS) can be measured in vitro by the mitotic rate and number of proliferating cells. In STS the grade of malignancy, in which the mitotic index plays a major role, is considered to be the major standard in predicting biological tumour behaviour. This study was designed to test the validity of TYR-PET in relation to different histopathological features. In 21 patients with untreated STS, the PSR was measured using TYR-PET. The number of mitoses was counted and tumours were graded according to the grading system of Coindre et al. (Cancer 1986; 58:306–309). Proliferative activity was assessed by immunohistological detection of the Ki-67 nuclear antigen using MIB-1 monoclonal antibody. To test the association between the PSR and these tumour parameters, a correlation analysis was performed. A significant (P<0.05) correlation was found between PSR and the Ki-67 proliferation index (R = 0.54), and between PSR and mitotic rate (R = 0.64). There was no correlation between PSR and tumour grade. The present study in malignant soft tissue tumours relates in vivo tumour metabolism as established with TYR-PET to tumour activity measured in vitro and indicates that the non-invasive method of TYR-PET can estimate the mitotic and proliferative activity in STS. Received 18 August and in revised form 24 November 1998     

Blood metabolism of [methyl- 11C]choline; implications for in vivo imaging with positron emission tomography

[methyl-¹¹C]Choline (¹¹C-choline) is a radioligand potentially useful for oncological positron emission tomography (PET). As a first step towards the development of a kinetic model for quantification of ¹¹C-choline uptake, blood metabolism of ¹¹C-choline during PET imaging was studied in humans. High-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) were used for the analysis of ¹¹C-choline and its radioactive metabolites. Prior to human PET imaging we studied ex vivo the biodistribution and metabolism of intravenously administered ¹¹C-choline in rats. Our results revealed that the radioactivity accumulated particularly in kidney, lung, adrenal gland and liver. Chromatographic analysis showed that the level of unmetabolized ¹¹C-choline in rat plasma decreased from 42%±20% (mean±SD) at 5 min to 21%±10% at 15 min after injection. In accordance with these findings, in humans the unmetabolized ¹¹C-choline represents 62%±19% of the total radioactivity in arterial plasma at 5 min after injection and 27%±12% at 15 min. In human venous plasma the corresponding values were 85%±12% and 48%±12% at 5 and 10 min, respectively. The major metabolite observed in both human and rat plasma was identified as ¹¹C-betaine. In human arterial plasma this maximally represented 82%±9% of the total radioactivity at 25 min after radiotracer injection. By 20 min after injection, the ¹¹C-choline and ¹¹C-betaine in human arterial plasma reached a plateau, and their fractional activities remained nearly constant thereafter. Although most of the circulating ¹¹C-choline in blood is transported to tissues, it does not disappear totally from blood within the first 40 min after tracer injection. Received 7 July and in revised form 16 September 1999     

11C-胆碱和18F-FDG在肿瘤PET中的比较

11C-胆碱是最近研制的一种正电子肿瘤阳性显像剂,在肿瘤/非靶组织的比值高于18F-FDG,特别在脑肿瘤和前列腺癌显像方面较18F-FDG显示出优势.11C-胆碱和18F-FDG在脑肿瘤、肺癌、食道癌和前列腺癌的诊断方面各有优劣,两者的摄取机理与显像方法也不同.除了11C-胆碱,还有18F-氟代胆碱(18F-fluorocholine),其临床价值有待更多的研究来证实.