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Purpose: Prostate cancer is the second leading cause of death from cancer among US men. Positron emission tomography (PET) with [(11)C]choline has been shown to be useful in the staging and detection of prostate cancer. The background of the increased uptake of choline in human prostate cancer is not completely understood. The aim of this study was to prospectively investigate the relationship between the [(11)C]choline uptake and the cell proliferation in human prostate cancer., Methods: Prostate cancer tissue from 18 patients who had undergone a radical prostatectomy for histologically proven disease was studied. An [(11)C]choline PET scan was performed prior to surgery. Post-prostatectomy specimens were prepared and stained with the antibody MIB-1 for Ki-67, which depicts proliferation. Two independent observers counted the amount of stained nuclei per specimen., Results: Prostate cancer showed Ki-67 staining and high uptake of [(11)C]choline. Statistical analysis showed no significant correlation between [(11)C]choline uptake and Ki-67 staining (R=0.23; P=0.34). No significant relationships were found between the uptake of [(11)C]choline (SUV) and either preoperative PSA (R=0.14; P=0.55) or Gleason sum score (R=0.28; P=0.25)., Conclusion: In vivo uptake of [(11)C]choline does not correlate with cell proliferation in human prostate cancer as depicted by Ki-67. Our results suggest that a process other than proliferation is responsible for the uptake of [(11)C]choline in prostate cancer.

Purpose: The beta-adrenoceptor (beta-AR) plays an important role in heart failure. Recently, the new tracer (S)-[11C]CGP12388 has been developed. It displays excellent properties for investigation of the cardiac beta-ARs in vivo with positron emission tomography (PET). Furthermore, the simple production method allows its use in a routine clinical setting. The aim of this study was to investigate whether decreased myocardial beta-AR density in patients with idiopathic dilated cardiomyopathy (IDC) can be estimated using (S)-[11C]CGP12388 PET., Methods: Myocardial beta-AR density was investigated in six patients with IDC and six age-matched healthy controls, using (S)-[11C]CGP12388 PET., Results: Beta-AR densities of 5.4+/-1.3 pmol/g (mean +/- SD) were observed in patients; these values were significantly lower than those observed in healthy controls (8.4+/-1.5 pmol/g, p<0.005)., Conclusion: This study indicates that PET with (S)-[11C]CGP12388 is applicable for the measurement of myocardial beta-AR density in patients. A highly significant reduction in beta-AR density was found in patients with IDC compared with healthy controls.

Fluorine-18 fluorodeoxyglucose (FDG), the most widely used radiopharmaceutical in positron emission tomography (PET) for oncological purposes, is unsuitable for imaging of bladder cancer owing to high excretion into the urine. More specific PET radiopharmaceuticals which are not excreted into urine would be welcome. Carbon-11 labelled choline (CHOL) is a new radiopharmaceutical potentially useful for tumour imaging and is not excreted into the urine. We prospectively studied the visualisation of bladder cancer using CHOL PET. Eighteen patients with bladder cancer and five healthy volunteers were included. Bladder cancer was first diagnosed by transurethral resection or by biopsy of the tumour. Next, PET images were performed before surgical treatment by cystectomy. The histopathological findings after cystectomy were used as the gold standard. PET images were performed on either an ECAT 951/31 or an ECAT Exact HR+ system. Attenuation-corrected PET images were obtained after injection of 400 MBq CHOL. PET images were analysed by two independent physicians using visual analysis and calculation of the standardised uptake value (SUV). In the normal bladder wall, the uptake of CHOL was low, and the bladder margin was only outlined by minimal urinary radioactivity, if present. In ten patients the tumour was detected correctly by CHOL PET, with an SUV of 4.7+/-3.6 (mean+/-SD). One false positive CHOL PET scan was seen in a patient with an indwelling catheter for 2 weeks prior to the PET scan. In two patients, lymph node metastases were detected by CHOL PET. A micrometastasis <5 mm was not visualised with CHOL PET. In seven patients, no residual tumour was found after surgery. In six of seven patients CHOL PET imaging was negative. In situ carcinoma, dysplasia and a non-invasive urothelial tumour (pTa) remained undetected in three of these six patients. Minimal to no urinary tract radioactivity was seen in 22/23 subjects. Non-specific uptake of CHOL was observed in the small bowel, rectum and prostate gland. CHOL uptake in bladder cancer was avid, visualising the tumour in the virtual absence of urinary radioactivity. No uptake of CHOL was seen in pre-malignant lesions or in small non-invasive tumours. Our results warrant further research into the value of CHOL PET in the clinical management of patients with bladder cancer.

Accurate assessment of tumour extent and lymph node involvement in squamous cell carcinomas of the head and neck region is essential for therapy planning. Unfortunately, conventional diagnostic examination and imaging techniques, which monitor tumours on the basis of anatomical parameters, have drawbacks in clinical practice. The aim of this study was to investigate the feasibility of L-[1-(11)C]-tyrosine (TYR) positron emission tomography (PET) for visualisation of squamous cell carcinoma of the larynx and hypopharynx and quantification of tumour activity by assessment of protein synthesis rate (PSR). Dynamic TYR PET was performed on 31 patients with T1-T4 laryngeal or hypopharyngeal carcinoma before therapy. Plasma activity of TYR, (11)CO(2) and (11)C-protein levels were measured, and PSRs were calculated for primary malignancies. All 31 laryngeal and hypopharyngeal tumours were visualised as a hotspot (sensitivity 100%). The median PSR of the tumours (2.06 nmol ml(-1) min(-1); range 0.72-6.96) was significantly higher ( P<0.001) than that of non-tumour (background) tissue (0.51 nmol ml(-1) min(-1); range 0.22-0.89). L-[1-(11)C]-Tyrosine PET appears to be a potential method for visualisation of primary laryngeal and hypopharyngeal tumours. In vivo quantification of tumour activity by assessment of PSR is possible and may have a future role in the therapy planning and therapy evaluation of laryngeal and hypopharyngeal tumours.

In 1%-2% of head and neck oncology patients, the only symptom of a malignancy is a positive cervical node. The aim of this study was to compare the value of positron emission tomography using fluorine-18 fluoro-2-deoxy- D-glucose (FDG-PET) and conventional diagnostic modalities (CT and/or MRI, panendoscopy) in detecting unknown primary tumours and distant metastases in patients suffering from such a cervical metastasis. Fifty patients (37 men and 13 women) with cervical metastases of an unknown primary tumour were included. All patients underwent FDG-PET. In addition, CT and/or MRI was obtained and panendoscopy was performed. All clinically known metastases were detected by FDG-PET. The primary tumour could be diagnosed in 16 patients (four primary tumours were detected exclusively by FDG-PET). Seven patients had multiple distant metastases, that in six cases were detected exclusively by FDG-PET. The sensitivity and specificity of FDG-PET for detection of unknown primary tumours were 100% and 94%, respectively. For the conventional diagnostic modalities these values were 92% and 76%. FDG-PET had an exclusive effect on the applied therapy in 20% of the patients referred for diagnosis of an unknown primary tumour. The data obtained in this study strongly support the diagnostic strategy of performing FDG-PET in patients suffering from cervical metastases of an unknown primary tumour before any other diagnostic technique.

The aim of this study was to determine whether the beta-adrenoceptor receptor density (Bmax) and the ligand affinity (KD) of (S)-[11C]CGP 12388 for the beta-adrenoceptor receptor could be determined using full tracer kinetic modelling of the transport of the ligand and its interaction with the receptor. This approach minimises the a priori assumptions and may thus serve as a gold standard to validate other simplified methods. Dynamic positron emission tomography (PET) data were acquired in six healthy subjects during 60 min. Three different injection protocols were applied, each consisting of three injections with varying SAs: high specific activity (SA), low SA or unlabelled ligand only. Arterial blood samples were collected via a cannula in the radial artery. Time-activity data in myocardial tissue were obtained using regions of interest (ROIs) on short-axis planes. All data were analysed with a two-tissue compartment, six-parameter (K1, k2, k(on), k(off), Bmax, F(bv)) model that relies on explicit compartments for describing the kinetics of both labelled and unlabelled radioligand. Time-activity curves showed that unlabelled ligand could displace the radioligand from the receptor. This resulted in increased radioactivity levels in plasma. Modelling results yielded Bmax values of 9.74+/-1.80 nM and a KD of 0.58+/-0.22 nM, assuming a reaction volume of 0.15. In addition, parametric polar images of Bmax could be calculated. The protocol with injections of high SA, low SA, and unlabelled ligand, respectively, was found to be the most sensitive to parameter changes. We conclude that with tracer kinetic modelling of (S)-[11C]CGP 12388, the beta-adrenoceptor density in the human heart can accurately be obtained in vivo. This approach may thus serve as a gold standard.

This study evaluated the potential role of L-(1-(11)C)-tyrosine positron emission tomography (TYR PET) for visualisation and quantification of protein metabolism in lung cancer. Dynamic TYR PET scans of the thorax were performed in 17 patients with lung cancer. Protein synthesis rate (PSR in micromol/min x l) and standardised uptake value (SUV, corrected for body measurements) of tumour tissue and contralateral normal tissue were calculated before and after chemotherapy or radiotherapy. All tumours [11 non-small cell lung carcinomas (NSCLCs), five small cell lung carcinomas (SCLCs), and one pleural mesothelioma] were visualised as a hot spot. The median PSR in tumour tissue was higher than that in corresponding contralateral normal lung tissue before [1.88 micromol/min x l (range 1.10-3.42) vs 0.40 micromol/min x l (range 0.12-0.86); P=0.003] and after treatment [1.33 micromol/min x l (range 0.45-2.21) vs 0.28 micromol/min x l (range 0.18-0.51); P<0.02]. In contrast to PSR of normal lung tissue, PSR of tumour tissue decreased significantly after therapy (P=0.03). Before therapy, no significant difference in PSR between NSCLCs and SCLCs was observed, but after therapy the PSR differed significantly between the subgroups [1.69 micromol/min x l (range 0.63-2.78) for NSCLC vs 0.67 micromol/min x l (range 0.45-0.92) for SCLC; P=0.03], irrespective of the treatment modality. The median SUV of tumour tissue was higher than that in corresponding contralateral normal lung both before and after therapy. Only a weak correlation between PSR and SUV was found when the latter was corrected for body surface area or lean body mass. Carbon-11 labelled tyrosine appears to be a good tracer for visualising lung cancer. PSR of tumour tissue can be used to quantify reduction in the metabolic rate of the tumour. Future studies need to be performed to determine whether TYR PET will supply additional clinical information with treatment implications in patients with lung cancer.