research article
Role of 18F-choline PET/CT in evaluation of patients with prostate carcinoma
Marina Hodolic
Department for Nuclear Medicine, University Medical Centre Ljubljana, Slovenia
Received 4 October 2010 Accepted 18 October 2010
Correspondence to: Marina Hodolič, MD, PhD, Department for Nuclear Medicine, University Medical Centre Ljubljana, Zaloška 7, Slovenia; Phone:+386 1 522 3548; Fax:+386 1 522 22 37; E-mail: marina.hodolic@kclj.si
Disclosure: No potential conflicts of interest were disclosed.
Background. Choline presents a high affinity for malignant prostate tissue. It can be labelled with positron emitting
18F, and used for the evaluation of patients with prostate carcinoma by PET/CT imaging. The aim of this paper is to summarise our experience with fluoromethylcholine (18F-choline) PET/CT in patients with prostate cancer. Methods. In 4 months we investigated the patients with histopathological (or cytological) confirmed prostate cancer. Two observers evaluated the early and late 18F-choline PET images in correlation with corresponding localising CT images and using the semiquantitative standard uptake value (SUV) calculation.
Results. The 18F-choline PET/CT was made in 50 patients with prostate cancer. There were 18 patients after radical prostatectomy and 32 without surgery. In all patients without surgery the pathological uptake was seen in the prostate. In 14 (44 %) patients of this group there was evidence of metastatic spread in local or distant lymph nodes and/or bones. In out of 18 patients after radical prostatectomy the local recurrence was detected in 6 patients (33%) and distant metastases were present in 2 patients (10%).
Conclusions. 18F-choline PET/CT seems to be useful imaging modality in patients with prostate carcinoma; it can demonstrate spread of the disease preoperatively and detect the local recurrence after radical prostatectomy.
Key words: prostate carcinoma; 18F-choline PET/CT; diagnosis; staging; follow-up
Introduction
Prostate carcinoma is the most common life-threatening cancer affecting men in the Western world. The mortality is around 10%. The major goals of pretherapeutic imaging are to determine the local extent of prostate carcinoma in terms of intrapros-tate localisation, extracapsular extension, seminal vesicle invasion, tumour infiltration into neurovas-cular bundles, surrounding tissues and organs in the small pelvis, detection of loco-regional metastases via the lymph nodes and detection of distant metastases. The exact pretherapeutic diagnosis and staging are essential, because the tumour treatment must be selected in strict dependence on the clinical tumour stage and risk profile.12
Both anatomic and functional molecular imaging of prostate carcinoma is important especially when there are problems with diagnosis, for example when prostate punch biopsies are negative while the suspicion of prostate carcinoma persists
(for example rising PSA). They may also be helpful in localising the carcinoma, revealing how the carcinoma relates to the surrounding intra- and ex-traprostatic structures and organs.
18F-Fluorodeoxyglucose (FDG) PET/CT is a nuclear medicine procedure currently most widely used to diagnose primary and metastatic cancers.3 Unfortunately, not all tumours show a significant increase of metabolic activity on 18F-FDG PET/CT imaging. This is particularly true for neuroendocrine tumours, hepatic tumours and prostate can-cer.4
Choline presents a high affinity for malignant prostate tissue, even if low grade. Choline can be labelled with either 11C or 18F, the former being the preference due to the lower urinary excretion and patients' exposure. The latter is more useful for a possible distribution to centres lacking in on-site cyclotron. The sensitivity of 18F-choline PET/CT to detect prostate cancer preoperatively is 73%, greater than with 18F-FDG PET/CT (31%). Also the accu-

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The aim of this paper is to summarise our experience with fluoromethylcholine (18F-choline) and PET/CT in patients with prostate cancer.
Patients and methods
From 12.05.2010 to 15.09.2010 months we investigated the patients with cytological or histological confirmed prostate cancer.
The patients were fasting 6-10 hours prior the scan. 18F-choline (IASOcholine® from IASON Austria) was injected i.v. (200 - 300 MBq, according to the weight of the patient) using the automatic radionuclide injector (Medrad). List mode acquisition over prostatic bed started immediately after the injection of the tracer and lasts for 5 minutes. After this early phase patients rested for approximately one hour. The whole body acquisition was performed thereafter, 2 min per bed position from base of the skull to midthigh (9 bed positions on average). Siemens Biograph mCT PET/CT scanner has been used.
Early images were reconstructed from the list mode acquisition study before the activity appeared in the bladder (Figure 1A). Early (0-5 min p.i) images and late (60 min p.i.) whole body images were presented in the usual transaxial, coronal and sagital planes. Two observers evaluated the images in correlation with corresponding localising CT images and using semiquantitative standard uptake value (SUV) calculation.
Results
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FIGURE 1. Prostate carcinoma: A prostatic bed (early images), B whole body (late images). Upper left panel: CT image. Upper right panel: fused PET/CT image. Lower left panel: PET image. Lower right panel: maximum intensity projection (MIP).
racy is greater with 18F-choline PET/CT (67%) than using 18F-FDG PET/CT (53%).5 The use of 18F-FDG in prostate cancer is limited to the most aggressive cancers.6
The 18F-choline PET-CT was performed in 50 patients with prostate cancer. The mean age was 67.7 years. There were 32 patients before radical prostatectomy and 18 after surgery (Table 1.).
The early phase has been used to evaluate prostate or prostate bed. The findings corresponded to late phase images in all patients (Figures 1 A, B). In patients with bony metastases in the pelvis the pathological uptake was seen in metastases already during the first 5 min after the tracer injection (Figures 2 A, B).
In all patients without surgery the pathological uptake was seen in the prostate. In 14 (44 %) patients of this group there was evidence of metastat-ic spread in local or distant lymph nodes (Figure 3) and/or bones (Figure 2 B). In patients after radical prostatectomy the local recurrence was detected in 6 patients (Figure 4) (33%) and distant metastases
TABLE 1. Results of 18F-choline PET/CT scans in 50 patients with prostate carcinoma
Number of patients Prostatic bed (positive)	Metastases (positive)
After radical prostatectomy 18 6 (33 %)	2 (10%]
No surgery 32 32 (100%)	14 (44%)
Total 50 38 (96%)	16 (33%)
were present in 2 patients one had also the local recurrence; the other one has no evidence of local recurrent disease (Table 1).
Discussion
Indications for 18F-choline PET/CT imaging modality in evaluation of patients with prostate cancer cover a wide spectrum of clinical settings: localisation of intraprostatic neoplastic lesions, initial staging, detection of occult recurrences and characterisation of images on conventional imaging modalities, which are questionable or difficult to interpret. 18F-choline is taken up by prostatic carcinoma as well as distant metastases very fast, already during 5 min after the injection (Figure 2).
The accurate knowledge of the normal biodistribution of 18F-choline is essential for the correct interpretation of PET/CT images. CT enables the differentiation of physiological bowel activity and 18F-choline excretion in the ureters. 18F-choline uptake in benign pathological conditions mainly includes sites of inflammation; nevertheless, the accumulation in tumour deposits not due to prostate cancer cannot be excluded.7
Similarly to FDG, choline is also taken up by in-fection.8 The differentiation between inflamed and metastatic lymph nodes can be achieved either by two phases PET or by appropriate antimicrobial treatment preceding 18F-choline PET/CT. On dualphase PET of the prostate, areas of malignancy consistently demonstrated the stable or increasing 18F-choline uptake, whereas most areas containing benign tissue demonstrated the decreasing uptake.
Delayed or dual-phase imaging after the injection of 18F-choline may improve the performance of 18F-choline PET for localising malignant areas of the prostate.9 18F-choline PET/CT showed a fast progressively increasing max. SUV in biopsy confirmed cancer lesions up to 14 min post injection while decreasing in inguinal lymph nodes interpreted as benign. Furthermore, it was very useful in differentiating local recurrences from confounding blood pool and urinary activity.10 Although more data need to be obtained, it appears that 18F-choline
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FIGURE 2. Bone metastases due to prostate cancer: A prostatic bed (early images), B whole body (late images). Upper left panel: CT image. Upper right panel: fused PET/CT image. Lower left panel: PET image. Lower right panel: maximum intensity projection (MIP).
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FIGURE 3. Lymph node metastases due to prostate cancer: whole body scan (late images). Upper left panel: CT image. Upper right panel: fused PET/CT image. Lower left panel: PET image. Lower right panel: maximum intensity projection (MIP).


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FIGURE 4. Relapse of prostate cancer: whole body (late images). Upper left panel: CT image. Upper right panel: fused PET/CT image. Lower left panel: PET image. Lower right panel: maximum intensity projection (MIP).
PET/CT is highly efficient in preoperative management regarding N and M staging of prostate cancer once metastatic disease is strongly suspected or documented.11 18F-choline PET/CT could be useful in the evaluation of patients with prostate cancer who are at high risk for extracapsular disease, and it could be used to preoperatively exclude distant metastases.12
Patients with persistent elevated PSA and repeated negative prostate biopsy, (i.e. prostate being biopsied at multiple times), were investigated with 18F-choline PET/CT to delineate prostate cancer and guide renewed prostate biopsy. In 25% of patients, 18F-choline PET/CT allowed the identification of neoplastic prostatic zones.13
The sensitivity, specificity and accuracy of 18F-choline PET/CT in the detection of bone metastases in prostate cancer are 74%, 99% and 85%, respectively. 18F-choline PET-CT may be superior to bone scintigraphy for the early detection of met-astatic bone disease due to the detection of bone marrow metastases.13
Out of all patients with carcinoma of the prostate undergoing therapeutic regimes with curative intent, 15-23% will ultimately relapse and 16-35% will need some sort of salvage therapy within 5 years. Of relapsing patients, 50% will have local recurrence and 50% systemic disease with or without local recurrence. Therefore, the localisation of recurrent prostate cancer is critical for selecting a local or systemic therapeutic strategy.15 Modern fusion imaging with 18F-choline PET/CT has augmented the diagnostic imaging spectrum for the assessment of relapsing prostate cancer. In 60-70% of patients with biochemical relapse, recurrent tumour can be detected and anatomically precisely localised. Imaging with 18F-choline PET/CT and MRI possesses a high potential for the early localisation of recurrent prostate carcinoma.16
In patients with biochemical relapse after the radical treatment for prostate cancer, 18F-choline PET/CT represents a single step, whole-body, non-invasive study that allows disease detection and localisation. Detection sensitivity is probably negatively correlated with serum PSA concentration. Pelosi et al. reported that 18F-choline PET scan detected the disease relapse in 42.9% of cases (24/56). PET sensitivity was 20% in the PSA < 1 ng/ml subgroup, 44% in PSA > 1 and < 5, and 81.8% in PSA > 5 ng/ml subgroup, respectively.17 According to other investigators 18F-choline 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, 18F-choline PET/CT helps to exclude distant metastases when the salvage local treatment is intended.18 Most probably doubling time of serum PSA increase is more important as PSA level itself.
18F-choline PET/CT seems to be useful also for the evaluation of other cancers with poor FDG uptake, such as hepatocellular carcinoma.19
Conclusions
In future studies some of dilemmas that appear in presented study need to be solved: to correlate PET/CT results with standard prognostic factors and to determine their prognostic significance (correlation of our PET/CT results with starting PSA, clinical T stage, Gleason score in surgically treated/ biopsied patients and PSA doubling time in patients with biochemical recurrence).
18F-choline PET/CT seems to be useful imaging modality in patients with prostate carcinoma for demonstrating the spread of the disease preoper-atively and to detect local recurrent disease after radical prostatectomy.
11.	Langsteger W, Heinisch M, Fogelman I. The role of fluorodeoxyglucose, 18F-dihydroxyphenylalanine, 18F-choline, and 18F-fluoride in bone imaging with emphasis on prostate and breast. Semin Nucl Med 2006; 36: 73-92.
12.	Beheshti M, Imamovic L, Broinger G, Vali R, Waldenberger P, Stoiber F, et al. 18F choline PET/CT in the preoperative staging of prostate cancer in patients with intermediate or high risk of extracapsular disease: a prospective study of 130 patients. Radiology 2010; 254: 925-33.
13.	Igerc I, Kohlfurst S, Gallowitsch HJ, Matschnig S, Kresnik E, Gomez-Segovia I, et al. The value of 18F-choline PET/CT in patients with elevated PSA-level and negative prostate needle biopsy for localisation of prostate cancer. Eur J Nucl Med Mol Imaging 2008; 35: 976-83.
14.	Beheshti M, Vali R, Waldenberger P, Fitz F, Nader M, Loidl W, et al. Detection of bone metastases in patients with prostate cancer by 18F fluorocholine and 18F fluoride PET-CT: a comparative study. Eur J Nucl Med Mol Imaging 2008; 35: 1766-74.
15.	Horvat AG, Kovac V, Strojan P. Radiotherapy in palliative treatment of painful bone metastases. Radiol Oncol 2009; 43: 213-24.
16.	Reske SN; Blumstein NM; Glatting G. PET and PET/CT in relapsing prostate carcinoma. Urologe A 2006; 45: 1240-50.
17.	Pelosi E, Arena V, Skanjeti A, Pirro V, Douroukas A, Pupi A, et al. Role of whole-body 18F-choline PET/CT in disease detection in patients with biochemical relapse after radical treatment for prostate cancer. Radiol Med 2008; 113: 895-904.
18.	Cimitan M, Bortolus R, Morassut S, Canzonieri V, Garbeglio A, Baresic T, et al. [18F]fluorocholine PET/CT imaging for the detection of recurrent prostate cancer at PSA relapse: experience in 100 consecutive patients. Eur J Nucl Med Mol Imaging 2006; 33: 1387-98.
19.	Yamamoto Y, Nishiyama Y, Kameyama R, Okano K, Kashiwagi H, Deguchi A, et al. Detection of hepatocellular carcinoma using 11C-choline PET: comparison with 18F-FDG PET. J Nucl Med 2008; 49: 1245-8.
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