[<Superscript>11</Superscript>C]choline PET/CT imaging in occult local relapse of prostate cancer after radical prostatectomy

Purpose The aim of this study was to assess the accuracy and clinical impact of [¹¹C]choline PET/CT for localizing occult relapse of prostate adenocarcinoma after radical prostatectomy. Methods Fourty-nine patients with prostate adenocarcinoma, radical prostatectomy, no evidence of metastatic disease, and occult relapse underwent [¹¹C]choline PET/CT. Thirty-six of the patients had biochemical evidence and histological evaluation of local recurrence. Thirteen patients had PSA < 0.3 ng/ml and no evidence of active disease after 1 year follow-up. Focal nodular [¹¹C]choline uptake in the prostatic fossa was visually assessed and graded on a five point scale. Maximum standardized radioactivity uptake value (SUV_max) and the lesion size were measured. A receiver operating characteristic (ROC) analysis was performed and the clinical impact of the PET/CT study was determined. Results [¹¹C]choline PET/CT was true positive in 23/33 patients and true negative in 12/13 controls. SUV_max of local recurrence was 3.0 (median, range 0.6–7.4) and 1.1 (0.4–1.6) in controls (p = 0.0002). Lesion size was 1.7 cm (range 0.9–3.7). Area under the ROC curve for detecting relapse was 0.90 ± 0.05 and 0.83 ± 0.06 for visual evaluation and SUV_max, respectively. Sensitivity and specificity of [¹¹C]choline PET/CT were 0.73 and 0.88, respectively. [¹¹C]choline PET/CT identified 12/17 (71%) patients with a favourable biochemical response to local radiotherapy at 2 year (median, 0.8–3.2 range) follow-up. Conclusions Focally increased [¹¹C]choline uptake in the prostatic bed reliably predicted local low volume occult relapsing prostate adenocarcinoma after radical prostatectomy and identified 71% of patients with a favourable biochemical response to local radiotherapy.     

(11)C]Choline positron emission tomography/computed tomography for staging and restaging of patients with advanced prostate cancer

INTRODUCTION: To evaluate [(11)C]Choline positron emission tomography (PET)/computed tomography (CT) for staging and restaging of patients with advanced prostate cancer and to compare the diagnostic performance of PET, CT and PET/CT. METHODS: Forty-five consecutive patients with advanced prostate cancer underwent [(11)C]Choline-PET/CT between 5/2004 and 2/2006. RESULTS: Overall, 295 lesions were detected: PET alone, 178 lesions; diagnostic CT, 221 lesions; PET/CT (low-dose CT), 272 lesions; PET/CT (diagnostic CT), 295 lesions. Two thirds of the lesions were located in the bone; one third in the prostate, lymph nodes, periprostatic tissue and soft tissue (lung, liver). The use of diagnostic CT did not result in a statistically significant difference with respect to lesion localization certainty and lesion characterization (P=.063, P=.063). PET-negative but PET/CT-positive lesions were mostly localized in the bone (78%, 91/117) as were PET-positive and CT-negative lesions (72%, 53/74). Of the latter, 91% (48/53) represented bone marrow and 9% (5/53) cortical involvement. CONCLUSIONS: Staging and restaging with [(11)C]Choline PET/CT in patients with advanced prostate cancer improve the assessment of local and regional recurrent as well as metastatic disease including skeletal manifestations. [(11)C]Choline PET/CT (with a low-dose CT) results in improved localization and lesion characterization. [(11)C]Choline PET/CT provides an added value for skeletal manifestations. [(11)C]Choline PET/CT changed disease management in 11 (24%) of 45 patients with advanced prostate cancer.     

[<Superscript>11</Superscript>C]Choline uptake with PET/CT for the initial diagnosis of prostate cancer: relation to PSA levels,tumour stage and anti-androgenic therapy

PURPOSE: The accuracy of positron emission tomography (PET)/CT with [(11)C]choline for the detection of prostate cancer is not well established. We assessed the dependence of [(11)C]choline maximum standardized uptake values (SUV(max)) in the prostate gland on cell malignancy, prostate-specific antigen (PSA) levels, Gleason score, tumour stage and anti-androgenic hormonal therapy. METHODS: In this prospective study, PET/CT with [(11)C]choline was performed in 19 prostate cancer patients who subsequently underwent prostatectomy with histologic sextant analysis (group A) and in six prostate cancer patients before and after anti-androgenic hormonal therapy (bicalutamide 150 mg/day; median treatment of 4 months; group B). RESULTS: In group A, based on a sextant analysis with a [(11)C]choline SUV(max) cutoff of 2.5 (as derived from a receiver-operating characteristic analysis), PET/CT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 72, 43, 64, 51 and 60%, respectively. In the patient-by-patient analysis, no significant correlation was detected between SUV(max) and PSA levels, Gleason score or pathological stage. On the contrary, a significant (P < 0.05) negative correlation was detected between SUV(max) and anti-androgenic therapy both in univariate (r (2) = 0.24) and multivariate (r (2) = 0.48) analyses. Prostate [(11)C]choline uptake after bicalutamide therapy significantly (P < 0.05) decreased compared to baseline (6.4 +/- 4.6 and 11.8 +/- 5.3, respectively; group B). CONCLUSION: PET/CT with [(11)C]choline is not suitable for the initial diagnosis and local staging of prostate cancer. PET/CT with [(11)C]choline could be used to monitor the response to anti-androgenic therapy.     

Carbon-11 acetate positron emission tomography can detect local recurrence of prostate cancer

We investigated the potential of [(11)C]acetate positron emission tomography (PET) to detect local recurrence in prostate cancer (PCA) in patients with increasing PSA following complete prostatectomy. A total of 31 patients were studied and compared with the results of transrectal ultrasound (TRUS) combined with biopsy and clinical follow-up. Whole-body PET scan was performed 5 min after injection of 0.8 GBq [(11)C]acetate and completed within 1 h. Focally increased tracer uptake below the urinary bladder or in an abdominal lymph node region was considered as relapse. TRUS followed by biopsy verified recurrence in 18 patients and ruled it out in 13 patients. PET demonstrated local recurrence in 15 out of the aforementioned 18 patients. PET also demonstrated distant lymph node involvement and bone metastases in five patients each. No focal [(11)C]acetate uptake was demonstrated in the prostate bed in patients with negative biopsy. These patients had no evidence of disease during 6 months of follow-up. In the subgroup of patients with PSA <2.0 ng/ml ( n=8), five patients had positive PET findings, with four of them verified by biopsy. It is concluded that [(11)C]acetate PET is a promising new tool for the diagnosis of PCA recurrence and can influence patient management.     

Choline PET/CT for imaging prostate cancer: an update

Whole-body positron emission tomography/computed tomography (PET/CT) with [¹¹C]- and [¹⁸F]-labeled choline derivates has emerged as a promising molecular imaging modality for the evaluation of prostate cancer. ¹¹C- and ¹⁸F-choline PET/CT are used successfully for restaging prostate cancer in patients with biochemical recurrence of disease after definitive therapy, especially when the serum prostate-specific antigen level is >1.0 ng/mL. ¹¹C- and ¹⁸F-choline PET/CT have more limited roles for the initial staging of prostate cancer and for the detection of tiny lymph node metastases due to the low spatial resolution inherent to PET. Overall, these modalities are most useful in patients with a high pre-test suspicion of metastatic disease. The following is a review of the current clinical roles of ¹¹C- and ¹⁸F-choline PET/CT in the management of prostate cancer.     

Predictive factors of [11C]choline PET/CT in patients with biochemical failure after radical prostatectomy

Purpose

Detection of recurrence in prostate cancer patients with biochemical failure after radical prostatectomy by [¹¹C]choline PET/CT depends on the prostate-specific antigen (PSA) level. The role of other clinical and pathological variables has not been explored.

Methods

A total of 2,124 prostate cancer patients referred to our Institution for [¹¹C]choline PET/CT from December 2004 to January 2007 for restaging of disease were retrospectively considered for this study. Inclusion criteria were: previous treatment by radical prostatectomy, and biochemical failure, defined as at least two consecutive PSA measurements of >0.2 ng/ml. These criteria were met for 358 patients. Binary logistic analysis was used to investigate the predictive factors of [¹¹C]choline PET/CT. PET/CT findings were validated using criteria based on histological analysis, and follow-up clinical and imaging data. Receiver operating characteristic (ROC) analysis was used to assess the performance of [¹¹C]choline PET/CT in relation to PSA levels.

Results

The mean PSA level was 3.77?±?6.94 ng/ml (range 0.23–45 ng/ml; median 1.27 ng/ml). PET/CT was positive for recurrence in 161 of 358 patients (45%). On an anatomical region basis, [¹¹C]choline pathological uptake was observed in lymph nodes (107/161 patients, 66%), prostatectomy bed (55/161 patients, 34%), and in the skeleton (46/161 patients, 29%). PET/CT findings were validated using histological criteria (46/358, 13%), and follow-up clinical and imaging criteria (312/358, 87%). Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were, respectively, 85%, 93%, 91%, 87%, and 89%. In multivariate analysis, high PSA levels, advanced pathological stage, previous biochemical failure and older age were significantly (P?<?0.05) associated with an increased risk of positive PET/CT findings. The percentage of positive scans was 19% in those with a PSA level between 0.2 and 1 ng/ml, 46% in those with a PSA level between 1 and 3 ng/ml, and 82% in those with a PSA level higher than 3 ng/ml. ROC analysis showed that PET/CT-positive and PET/CT-negative patients could be best distinguished using a PSA cut-off value of 1.4 ng/ml.

Conclusions

In addition to PSA levels, pathological stage, previous biochemical failure and age should be considered by physicians when referring prostate cancer patients with biochemical failure after radical prostatectomy to [¹¹C]choline PET/CT.     

Positron emission tomography for prostate, bladder, and renal cancer

Prostate cancer, renal cancer, bladder, and other urothelial malignancies make up the common tumors of the male genitourinary tract. For prostate cancer, common clinical scenarios include managing the patient presenting with 1) low-risk primary cancer; 2) high-risk primary cancer; 3) prostate-specific antigen (PSA) recurrence after apparently successful primary therapy; 4) progressive metastatic disease in the noncastrate state; and 5) progressive metastatic disease in the castrate state. These clinical states dictate the appropriate choice of diagnostic imaging modalities. The role of positron emission tomography (PET) is still evolving but is likely to be most important in determining early spread of disease in patients with aggressive tumors and for monitoring response to therapy in more advanced patients. Available PET tracers for assessment of prostate cancer include FDG, 11C or 18F choline and acetate, 11C methionine, 18F fluoride, and fluorodihydrotestosterone. Proper staging of prostate cancer is particularly important in high-risk primary disease before embarking on radical prostatectomy or radiation therapy. PET with 11C choline or acetate, but not with FDG, appears promising for the assessment of nodal metastases. PSA relapse frequently is the first sign of recurrent or metastatic disease after radical prostatectomy or radiation therapy. PET with FDG can identify local recurrence and distant metastases, and the probability for a positive test increases with PSA. However, essentially all studies have shown that the sensitivity for recurrent disease detection is higher with either acetate or choline as compared with FDG. Although more data need to be gathered, it is likely that these two agents will become the PET tracers of choice for staging prostate cancer once metastatic disease is strongly suspected or documented. 18F fluoride may provide a more sensitive bone scan and will probably be most valuable when PSA is greater than 20 ng/mL in patients with high suspicion or documented osseous metastases. Several studies suggest that FDG uptake in metastatic prostate cancer lesions reflects the biologic activity of the disease. Accordingly, FDG can be used to monitor the response to chemotherapy and hormonal therapy. Androgen receptor imaging agents like fluorodihydrotestosterone are being explored to predict the biology of treatment response for progressive tumor in late stage disease in castrated patients. The assessment of renal masses and primary staging of renal cell carcinoma are the domain of helical CT. PET with FDG may be helpful in the evaluation of "equivocal findings" on conventional studies, including bone scan, and also in the differentiation between recurrence and posttreatment changes. The value of other PET tracers in renal cell carcinoma is under investigation. Few studies have addressed the role of PET in bladder cancer. Because of its renal excretion, FDG is not a useful tracer for the detection of primary bladder tumors. The few studies that investigated its role in the detection of lymph node metastases at the time of primary staging were largely disappointing. Bladder cancer imaging with 11C choline, 11C methionine, or 11C- acetate deserves further study.     

Imaging of a thymoma incidentally detected by C-11 choline PET/CT

The integrated modality positron emission tomography/computed tomography (PET/CT) with C-11 choline is an established diagnostic tool for restaging prostate cancer patients with a biochemical failure after primary treatment. Thymoma is a rare tumor originating in thymus epithelial cells, asymptomatic in one-third to one-half of patients, and often occurring in the fourth and fifth decades of life. In the present case, C-11 choline PET/CT was performed in a prostate cancer patient with a biochemical relapse, to restage the disease. In addition to the detection of local recurrent disease in prostatic fossa, an abnormal C-11 choline increased uptake in mediastinum was reported. The mediastinal finding was initially wrongly interpreted by clinicians as a lymph nodal metastasis from prostate cancer. However, histopathological analysis confirmed the presence of a thymoma. Although rare, thymoma has to be considered as differential diagnosis in case of mediastinal masses presenting C-11 choline PET/CT positive findings, to avoid inappropriate patient management.     

Unexpected finding of elevated glucose uptake in fibrous dysplasia mimicking malignancy: contradicting metabolism and morphology in combined PET/CT

Fibrous dysplasia is a common benign disorder of bone in which fibro-osseous tissue replaces bone spongiosa. Lesions have a typical appearance on computed tomography (CT) images and regularly show a markedly increased uptake in bone scintigraphy using ^99mTc-labelled methylene diphosphonate (^99mTc-MDP) as radiotracer. The glucose avidity of these lesions depicted by positron emission tomography (PET) using the radiolabelled glucose derivative ¹⁸F-fluoro-2-deoxy-glucose (FDG) is less well known since FDG-PET does not have a role in the assessment of this disease. However, single cases have been reported in which fibrous dysplasia was present in patients undergoing FDG-PET scanning for oncological reasons, and no significant FDG uptake was observed for lesions identified as fibrous dysplasia. We report on a 24-year-old man with known fibrous dysplasia who underwent combined FDG-PET/CT scanning because of suspected recurrence of testicular cancer. In contrast to prior reports, a markedly elevated uptake of FDG was seen in numerous locations that were identified as fibrous dysplasia by CT. Based on this result, we conclude that fibrous dysplasia may mimick malignancy in FDG-PET and that coregistered CT may help to resolve these equivocal findings.     

Experience with carbon-11 choline positron emission tomography in prostate carcinoma

We investigated the potential of carbon-11 choline positron emission tomography (PET) for the detection of lymph node and bone metastases in prostate cancer. A total of 23 patients were studied (known metastases: 8; suspicion of metastases: 3; primary staging: 12). Whole-body PET imaging was performed 5 min after injection of the tracer and completed within 1 h. Focally increased tracer uptake in bone or abdominal lymph node regions was interpreted as representing tumour involvement. All known bone and lymph node metastases could be recognized by [11C]choline PET. One out of ten negative scans for primary staging was false-negative (lymph node <1 cm) and one out of two positive scans was false-positive with regard to lymph node involvement (focal bowel activity). It is concluded that [11C]choline PET is a promising new tool for the primary staging of prostate cancer, with lymph node and bone metastases demonstrating high tracer uptake. Therapeutic management could be influenced by these results in that the technique may permit avoidance of surgical lymph node exploration.     

Choline PET/CT for prostate cancer: Main clinical applications

Several studies investigated the potential roles of imaging modalities in prostate cancer patients for the evaluation of intra-prostatic disease, stage and restage. However no precise guidelines exist about the use of imaging modalities, in particular about the role of PET/CT hybrid imaging. Considering the results of the literature and our experience, we tried to summarize the main applications of choline positron emission tomography (PET) in prostate cancer patients. The use of choline PET/CT for initial diagnosis and staging is not recommended as a first-line method. Instead the main and important application of choline PET/CT is represented by the restaging of the disease in case of biochemical relapse for the detection of lymph node and distant recurrence. In particular choline PET/CT could play a crucial role as first diagnostic procedure in prostate cancer patients who show a fast growing Prostate Specific Antigen (PSA) kinetics.     

Prostate carcinoma: diffusion-weighted imaging as potential alternative to conventional MR and 11C-choline PET/CT for detection of bone metastases

In a technical development study approved by the institutional ethics committee, the feasibility of fast diffusion-weighted imaging as a replacement for conventional magnetic resonance (MR) imaging sequences (short inversion time inversion recovery [STIR] and T1-weighted spin echo [SE]) and positron emission tomography (PET)/computed tomography (CT) in the detection of skeletal metastases from prostate cancer was evaluated. MR imaging and carbon 11 ((11)C) choline PET/CT data from 11 consecutive prostate cancer patients with bone metastases were analyzed. Diffusion-weighted imaging appears to be equal, if not superior, to STIR and T1-weighted SE sequences and equally as effective as (11)C-choline PET/CT in detection of bone metastases in these patients. Diffusion-weighted imaging should be considered for further evaluation and comparisons with PET/CT for comprehensive whole-body staging and restaging in prostate and other cancers.     

Experience with carbon-11 choline positron emission tomography in prostate carcinoma

We investigated the potential of carbon-11 choline positron emission tomography (PET) for the detection of lymph node and bone metastases in prostate cancer. A total of 23 patients were studied (known metastases: 8; suspicion of metastases: 3; primary staging: 12). Whole-body PET imaging was performed 5 min after injection of the tracer and completed within 1 h. Focally increased tracer uptake in bone or abdominal lymph node regions was interpreted as representing tumour involvement. All known bone and lymph node metastases could be recognized by [¹¹C]choline PET. One out of ten negative scans for primary staging was false-negative (lymph node <1 cm) and one out of two positive scans was false-positive with regard to lymph node involvement (focal bowel activity). It is concluded that [¹¹C]choline PET is a promising new tool for the primary staging of prostate cancer, with lymph node and bone metastases demonstrating high tracer uptake. Therapeutic management could be influenced by these results in that the technique may permit avoidance of surgical lymph node exploration.     

PET/CT characterization of fibroosseous defects in children: 18F-FDG uptake can mimic metastatic disease

OBJECTIVE: The purpose of this study was to characterize the anatomic appearance and metabolic activity of nonossifying fibromas, fibrous cortical defects, and cortical desmoids on PET/CT images. CONCLUSION: Over a 14-month period, we identified eight nonossifying fibromas, four fibrous cortical defects, and two cortical desmoids in 330 children who underwent PET/CT for the evaluation of a known or suspected malignancy. CT, conventional radiography, MRI, or clinical follow-up was used to confirm the diagnoses of these fibroosseous lesions. Eleven of the 14 children underwent multiple PET/CT examinations; thus, 34 studies were included. The lesions showed variable metabolic activity as indicated by 18F-FDG uptake: 19 PET/CT examinations showed lesions with mild 18F-FDG uptake, eight showed moderate 18F-FDG uptake, and seven showed intense uptake. When PET reveals metabolically active osseous abnormalities in children who are at risk for bone metastases, benign fibroosseous lesions should be considered in the differential diagnosis before additional diagnostic procedures are undertaken. Benign fibroosseous lesions may be metabolically active and thus mimic metastatic osseous disease in children with underlying malignancies. Correlative CT or other anatomic imaging can confirm the benign nature of these lesions.     

Nuclear medicine studies of the prostate, testes, and bladder

During the last decade, there has been a significant advancement in imaging of urologic diseases. Transrectal ultrasound (TRUS), computerized tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET) are still experiencing new developments in urology. Despite these many technological advances, the initial diagnostic procedure for a patient with suspected prostate cancer (PC) is multiple site blind prostate biopsies. There is a need for a noninvasive metabolic imaging modality to direct the site of biopsy to decrease the sampling error. MRS seems promising but as it is a costly and more time-consuming test, further studies are needed to evaluate its clinical utility. Currently, PET does not play any role to direct biopsy. Acetate and choline appear to be better tracers than FDG for the detection of a prostate lesion, however, further well-organized studies are needed before any of these agents can be used clinically. Incidental detection of intense focal uptake in the prostate during whole body PET scanning should be evaluated with prostate-specific antigen (PSA) and TRUS-guided biopsy. Although FDG is inferior to other tracers for primary staging, it may be useful in selected patients with suspected high-grade cancer. The role of ProstaScint scan is still controversial for detection of recurrent PC. This study may be helpful for evaluating nodal metastases when PSA is elevated and bone scan is negative. Bone scan remains the study of choice when bone metastases are suspected (PSA>15-20 ng/mL+/-bone pain). Acetate and choline provide better accuracy than FDG in the detection of local soft tissue disease, nodal involvement, and distant metastases. High FDG uptake may be indicative of more aggressive and possibly androgen-independent disease. PET/CT with any of the above PET tracers will most likely be preferred to the PET scan alone due to better localization of a hot lesion in PET/CT. Nuclear medicine studies also have been used to evaluate acute scrotum and testicular neoplasms. Scrotal scintigraphy has lost its popularity to Doppler ultrasound in the evaluation of the acute scrotum. In testicular tumors, FDG-PET appears to be superior to conventional imaging modalities in initial staging, detection of residual/recurrence, and monitoring treatment response. Tumor markers after treatment occasionally are elevated and cannot locate the site of recurrence, FDG-PET can play a very important role in this regard. Nuclear medicine studies also have been used to evaluate diseases of the urinary bladder. Radionuclide cystography is more sensitive and has less than 1/20 the radiation exposure of the conventional contrast enhanced micturating cystourethrogram (MCU). However, the utility of FDG-PET in the evaluation of bladder cancer seems to be limited to the evaluation of distant metastases. 11C-Methionine and choline may be a better option for local and nodal disease due to their negligible excretion in the urine.     

The detection rate of [<Superscript>11</Superscript>C]Choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer

Purpose An increase of the serum PSA-level is a sensitive in vitro marker for recurrent prostate cancer. However, it remains difficult to differentiate between local, regional or distant recurrent disease. The aim of this study was to assess the relationship between the detection rate of [¹¹C]Choline-PET/CT and the serum PSA-level in patients with a biochemical recurrence of prostate cancer with the view towards localisation of recurrent disease. Methods Sixty-three patients (mean age, 68.8 ± 6.9; range, 45–83 years) with biochemical recurrence after primary therapy for prostate cancer were included in the analysis. Mean PSA-levels were 5.9 ± 9.7 ng/ml (range, 0.2–39 ng/ml; median, 2.15). Of the 63 patients, 17 were under anti-androgen therapy at the time of [¹¹C]Choline PET/CT. Patients underwent a [¹¹C]Choline-PET/CT study after injection of 656 ± 119 MBq [¹¹C]Choline on a Sensation 16 Biograph PET/CT scanner. Results Of the 63 patients, 35 (56%) showed a pathological [¹¹C]Choline uptake. The detection rate of [¹¹C]Choline-PET/CT showed a relationship with the serum PSA-level: The detection rate was 36% for a PSA-value <1 ng/ml, 43% for a PSA-value 1–<2 ng/ml, 62% for a PSA-value 2–<3 ng/ml and 73% for a PSA-value ≥3 ng/ml. Anti-androgen therapy did not show a significant effect on the detection rate of [¹¹C]Choline-PET/CT (p = 0.374). Conclusion As an important result our study shows that even for PSA-values <1.0 ng/ml the detection efficiency of [¹¹C]Choline-PET/CT is 36%. Furthermore, the detection rate of [¹¹C]Choline-PET/CT shows a positive relationship with serum PSA-levels in patients with biochemical recurrence of prostate cancer after primary therapy. Therefore, in these patients, [¹¹C]Choline PET/CT allows not only to diagnose but also to localise recurrent disease with implications on disease management (localised vs systemic therapy).     

Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers.

Elevated levels of choline (trimethyl-2-hydroxyethylammonium) and choline kinase (CK) activity in neoplasms have motivated the development of positron-labeled choline analogs for noninvasive detection of cancer using PET. The aim of this study was to further evaluate [(18)F]fluorocholine (fluoromethyl-dimethyl-2-hydroxyethylammonium [FCH]) as an oncologic probe in comparison with several other closely related molecules. METHODS: FCH, [(18)F]fluoromethyl-methylethyl-2-hydroxyethylammonium (FMEC), [(18)F]fluoroethyl-dimethyl-2-hydroxyethylammonium (FEC), and [(18)F]fluoropropyl-dimethyl-2-hydroxyethylammonium (FPC) were synthesized through [(18)F]fluoroalkylation reactions. In vitro phosphorylation rates of the (18)F-labeled choline analogs and [methyl-(14)C]choline (CH) were studied using yeast CK. Several choline radiotracers were also evaluated in cultured PC-3 human prostate cancer cells. Data on chemical stability, radiation dosimetry, and toxicity of FCH were obtained. PET studies with FCH were performed on a patient with prostate cancer and a patient with a brain tumor. RESULTS: FCH and FMEC revealed in vitro phosphorylation by CK that was similar to that of choline, whereas rates of phosphorylation of FEC and FPC were 30% (P < 0.01) and 60% (P < 0.01) lower, respectively. Accumulations of FCH, CH, and FPC in cultured PC-3 cancer cells were comparable, whereas uptake of FEC was approximately one fifth that of FCH. Dosimetry estimates using FCH biodistribution data in mice indicated that the kidneys are radiation-dose-critical organs for FCH. PET images of a patient with recurrent prostate cancer showed uptake of FCH in the prostatic bed and in metastases to lymph nodes. FCH PET showed uptake in malignancies in a patient with metastatic breast cancer. PET revealed FCH uptake in biopsy-proven recurrent brain tumor with little confounding uptake by normal brain tissues. CONCLUSION: The fluoromethyl choline analog FCH may serve as a probe of choline uptake and phosphorylation in cancer cells, whereas fluoroethyl (FEC) and fluoropropyl (FPC) analogs appear to have relatively poorer biologic compatibility. Preliminary PET studies on patients with prostate cancer and with breast cancer and brain tumor support further studies to evaluate the usefulness of FCH as an oncologic probe.     

Comparison of integrated whole-body [11C]choline PET/MR with PET/CT in patients with prostate cancer

Purpose

To evaluate the performance of conventional [¹¹C]choline PET/CT in comparison to that of simultaneous whole-body PET/MR.

Methods

The study population comprised 32 patients with prostate cancer who underwent a single-injection dual-imaging protocol with PET/CT and subsequent PET/MR. PET/CT scans were performed applying standard clinical protocols (5 min after injection of 793?±?69 MBq [¹¹C]choline, 3 min per bed position, intravenous contrast agent). Subsequently (52?±?15 min after injection) PET/MR was performed (4 min per bed position). PET images were reconstructed iteratively (OSEM 3D), scatter and attenuation correction of emission data and regional allocation of [¹¹C]choline foci were performed using CT data for PET/CT and segmented Dixon MR, T1 and T2 sequences for PET/MR. Image quality of the respective PET scans and PET alignment with the respective morphological imaging modality were compared using a four point scale (0–3). Furthermore, number, location and conspicuity of the detected lesions were evaluated. SUVs for suspicious lesions, lung, liver, spleen, vertebral bone and muscle were compared.

Results

Overall 80 lesions were scored visually in 29 of the 32 patients. There was no significant difference between the two PET scans concerning number or conspicuity of the detected lesions (p not significant). PET/MR with T1 and T2 sequences performed better than PET/CT in anatomical allocation of lesions (2.87?±?0.3 vs. 2.72?±?0.5; p?=?0.005). The quality of PET/CT images (2.97?±?0.2) was better than that of the respective PET scan of the PET/MR (2.69?±?0.5; p?=?0.007). Overall the maximum and mean lesional SUVs exhibited high correlations between PET/CT and PET/MR (ρ?=?0.87 and ρ?=?0.86, respectively; both p?<?0.001).

Conclusion

Despite a substantially later imaging time-point, the performance of simultaneous PET/MR was comparable to that of PET/CT in detecting lesions with increased [¹¹C]choline uptake in patients with prostate cancer. Anatomical allocation of lesions was better with simultaneous PET/MR than with PET/CT, especially in the bone and pelvis. These promising findings suggest that [¹¹C]choline PET/MR might have a diagnostic benefit compared to PET/CT in patients with prostate cancer, and now needs to be further evaluated in prospective trials.     

PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, (18)F-fluorodeoxyglucose (FDG), is not very useful in the imaging of prostate cancer. However, in recent years other PET tracers have improved the accuracy of PET/CT imaging of prostate cancer. Among these, choline labeled with (18)F or (11)C, (11)C-acetate, and (18)F-fluoride has demonstrated promising results, and other new radiopharmaceuticals are under development and evaluation in preclinical and clinical studies. Large prospective clinical PET/CT trials are needed to establish the role of PET/CT in prostate cancer patients. Because there are only limited available therapeutic options for patients with advanced metastatic prostate cancer, there is an urgent need for the development of more effective treatment modalities that could improve outcome. Prostate cancer represents an attractive target for radioimmunotherapy (RIT) for several reasons, including pattern of metastatic spread (lymph nodes and bone marrow, sites with good access to circulating antibodies) and small volume disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Antiprostate-specific membrane antigen RIT demonstrates antitumor activity and is well tolerated. Clinical trials are underway to further improve upon treatment efficacy and patient selection. This review focuses on the recent advances of clinical PET/CT imaging and RIT of prostate cancer.     

11C-acetate PET imaging of prostate cancer: detection of recurrent disease at PSA relapse.

Patients with rising prostate-specific antigen (PSA) levels after definitive local therapy of prostate carcinoma present a diagnostic dilemma. A local recurrence would be amenable to additional local therapy with curative intent, whereas metastatic disease would require palliative androgen ablation therapy. In this study, we evaluated the effectiveness of PET with (11)C-acetate (AC PET) for evaluation of patients with rising PSA after radical prostatectomy or radiation therapy. We also compared the reliability of AC PET in detecting recurrent prostate cancer with that of PET with (18)F-FDG. METHODS: Two groups of patients with PSA recurrence were enrolled in this study: group A, 30 patients after prostatectomy, and group B, 16 patients after radiation therapy. After administration of 1,110 MBq (30 mCi) of (11)C-acetate, whole-body PET images were obtained. After allowing for (11)C decay, 555 MBq (15 mCi) of (18)F-FDG were administered and repeated whole-body imaging was performed. The PET findings were scored as positive or negative in each of the following regions: prostatic bed, pelvic nodes, paraaortic nodes, and other sites (bone or soft tissue). PET findings were correlated with those of CT, bone scintigraphy, and biopsy. RESULTS: Twenty-seven of 46 AC PET studies (59%) had positive findings, whereas only 8 (18)F-FDG PET studies had positive findings (17%). Limiting the analysis to patients with findings confirmed by CT, bone scintigraphy, or biopsy or considered highly likely to represent tumor, 14 (30%) had disease identified by AC PET, whereas only 4 (9%) had disease identified by (18)F-FDG PET. CT was performed on 22 patients and had positive findings in 3 (14%). Thirteen of 22 patients (59%) with serum PSA > 3 ng/mL had positive AC PET findings, whereas only 1 of 24 patients (4%) with serum PSA levels < or = 3 ng/mL had positive findings. CONCLUSION: AC PET demonstrates marked uptake in prostate cancer and has higher sensitivity than (18)F-FDG PET. These preliminary data show that (11)C-acetate is a promising tracer for detection of recurrent prostate cancer.