Carbon-11 choline has recently been introduced as a potential tracer for tumour imaging with positron emission tomography (PET). We evaluated the kinetics of the uptake of [(11)C]choline in prostate cancer and benign prostatic hyperplasia. We also evaluated the association between the uptake of [(11)C]choline and the histological grade of malignancy, Gleason score, volume of the prostate and prostate-specific antigen (PSA). Fourteen patients with histologically confirmed prostate cancer and five patients with benign prostatic hyperplasia were studied with [(11)C]choline PET. A mean dose of 430+/-31 MBq of [(11)C]choline was injected intravenously and a dynamic emission acquisition of prostate was performed for 30 min. The uptake of [(11)C]choline was measured as a standardised uptake value (SUV) and as a kinetic influx constant ( K(i)) obtained from graphical analysis. Both cancerous and hyperplastic prostate were well visualised with [(11)C]choline against low or moderate tracer accumulation in the bladder and rectal wall. The measured radioactivity in urine was invariably low. In the graphical analysis, linear plots were achieved. The mean K(i) of the untreated tumour was 0.205+/-0.089 min(-1) (range 0.128-0.351; n=7) and the mean SUV was 5.6+/-3.2 (range 1.9-15.5; n=15). K(i) values and SUVs correlated closely ( r=0.964, P=0.0005), whereas no correlation could be demonstrated between the tumour uptake of [(11)C]choline and the histological grade, Gleason score, volume of the prostate or PSA. The mean SUV and the mean K(i) of benign hyperplastic prostate were 3.5+/-1.0 (range 2.0-4.5; n=4) and 0.119+/-0.076 min(-1) (range 0.065-0.173; n=2). In conclusion, a high uptake of [(11)C]choline characterises not only carcinomatous but also hyperplastic prostatic tissue. Dynamic imaging of the uptake of [(11)C]choline in the prostate shows a good applicability of the graphical analysis model with an irreversible compartment. A close correlation between the K(i) values and semiquantitative SUVs of tumours supports the use of the simpler SUV in the clinical setting.

[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.

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[N-methyl-11C]alpha-Methylaminoisobutyric acid (11C-MeAIB) is a potentially useful tracer for positron emission tomography (PET) studies on hormonally regulated system A amino acid transport. 11C-MeAIB is a metabolically stable amino acid analogue specific for system A amino acid transport. We evaluated the biodistribution of 11C-MeAIB in rats and humans to estimate the usefulness of the tracer for in vivo human PET studies, for example, on regulation of system A amino acid transport and on tumour imaging. Healthy Sprague-Dawley rats (n=14) were killed 5, 20, 40 or 60 min after the injection of 11C-MeAIB, and the tissue samples were weighed and counted for 11C radioactivity. Ten lymphoma patients with relatively limited tumour burden underwent whole-body (WB) PET imaging with 11C-MeAIB. In addition, three other patients had dynamic PET scanning of the head and neck area, and the tracer uptake was quantitated by calculating the kinetic influx constants (Ki values) for the tracer. In animal studies, the highest activity was detected in the kidney, pancreas, adrenal gland and intestines. In humans, the highest activity was found in the salivary glands, and after that in the kidney and pancreas, similar to the results in animal studies. Rapid uptake was also detected in the skeletal muscle. In the graphical analysis, linear plots were obtained, and the mean fractional tracer uptake values (Ki) of the parotid glands (n=3) and cervical muscles (n=3) were 0.039+/-0.008 min(-1) and 0.013+/-0.006 min(-1), respectively. The Ki value of the tumour (n=1) was 0.064 min(-1). Higher uptake of 11C-MeAIB into the tumour tissue was encountered. These results encourage further 11C-MeAIB PET studies in humans on the physiology and pathology of system A amino acid transport and on tumour detection.

Amino acid transport system A is expressed strongly in neoplastic cells. [ N-methyl-(11)C]alpha-Methylaminoisobutyric acid ((11)C-MeAIB) is a recently developed tracer for PET studies on system A amino acid transport. (11)C-MeAIB is a metabolically stable amino acid analogue which is transported from plasma into the tissue by system A. This study evaluated the kinetics of (11)C-MeAIB uptake from plasma into tumour tissue and normal tissues in 13 patients with untreated head and neck cancer. (11)C-MeAIB uptake in tumour was compared with histological grade and proliferative activity. Tracer uptake was quantitated by calculating the standardised uptake values (SUVs) and the kinetic influx constants ( K(i)) using graphical analysis. All tumours accumulated (11)C-MeAIB and were visualised clearly. In the graphical analysis, linear plots were achieved; the mean K(i) value of tumour was 0.056+/-0.026 min(-1), and the mean SUV was 6.1+/-2.7. A close correlation between graphically obtained K(i) and semi-quantitative SUV in tumours was found ( r=0.887, P=0.00005). We could not demonstrate a correlation between the uptake of (11)C-MeAIB and the grade of malignancy or the proliferative index, as assessed using Ki-67 immunohistochemical assay. Head and neck cancer can be effectively imaged with (11)C-MeAIB PET. (11)C-MeAIB showed active and rapid transport into tumour tissue and salivary glands. Further studies on the applicability of (11)C-MeAIB PET for radiation treatment planning in the head and neck region and the regulation of system A amino acid transport under different metabolic states are warranted.

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Biodistribution of [11C]MeAIB in the abdominal region reflected the high activity of the transportation of amino acids via system A and these organs also had the highest radiation doses. An effective dose of 0.004 mSv/MBq is fully justified when [11C]MeAIB PET is performed to study system A activity in vivo.