Evaluation of [<Superscript>18</Superscript>F]-choline PET/CT for staging and restaging of prostate cancer

Purpose To evaluate the accuracy of [¹⁸F]-choline (FCH) positron emission tomography/computed tomography (PET/CT) for staging and restaging of prostate cancer. Methods FCH PET/CT was performed in 111 patients with prostate cancer using 200 MBq FCH: 43 patients [mean age 63 years; mean prostrate specific antigen (PSA) 11.58 μg/l] were examined for initial staging, and 68 patients (mean age 66.4 years) were examined for restaging (mean PSA 10.81 μg/l). FCH PET/CT results were correlated to histopathology, bone scan, morphology as revealed by magnetic resonance imaging (MRI) and CT, PET/CT follow-up and PSA follow-up after therapy. Results FCH PET/CT scans at initial staging correctly showed no metastases in 36/38 patients undergoing radical surgery, as confirmed by PSA levels <0.1 μg/l 6 months postoperatively. Lymphadenectomy was performed in 24 of these patients, revealing four false FCH-negative lymph nodes (LN). In one patient, only lymphadenectomy was performed since a FCH-positive LN was confirmed by histology. Four patients showed FCH-positive bone metastases, as proven by bone scan. FCH PET/CT scans at restaging correctly revealed local recurrence in 36 patients. No pathological FCH uptake was observed in 11 patients with biochemical recurrence. Twenty-three patients showed FCH-positive LN. Twenty LN were surgically removed in seven patients. Histopathology verified metastases in all LN, but revealed two additional metastastic, FCH-negative LN. Seventeen patients showed FCH-positive bone metastases, as proven by bone scan or MRI. Sensitivity to detect recurrent disease was 86%. Conclusion The results obtained using FCH PET/CT scans for initial N-staging were discouraging, especially in terms of its inability to detect small metastases. Recurrent disease can be localized reliably in patients with PSA levels of >2 μg/l.     

First imaging results of an intraindividual comparison of 11C-acetate and 18F-fluorocholine PET/CT in patients with prostate cancer at early biochemical first or second relapse after prostatectomy or radiotherapy

Purpose

¹⁸F-Fluorocholine (FCH) and ¹¹C-acetate (ACE) PET are widely used for detection of recurrent prostate cancer (PC). We present the first results of a comparative, prospective PET/CT study of both tracers evaluated in the same patients presenting with recurrence and low PSA to compare the diagnostic information provided by the two tracers.

Methods

The study group comprised 23 patients studied for a rising PSA level after radical prostatectomy (RP, 7 patients, PSA ≤3 ng/ml), curative radiotherapy (RT, 7 patients, PSA ≤5 ng/ml) or RP and salvage RT (9 patients, PSA ≤5 ng/ml). Both FCH and ACE PET/CT scans were performed in a random sequence a median of 4 days (range 0 to 11 days) apart. FCH PET/CT was started at injection (307?±?16 MBq) with a 10-min dynamic acquisition of the prostate bed, followed by a whole-body PET scan and late (45 min) imaging of the pelvis. ACE PET/CT was performed as a double whole-body PET scan starting 5 and 22 min after injection (994?±?72 MBq), and a late view (45 min) of the prostate bed. PET/CT scans were blindly reviewed by two independent pairs of two experienced nuclear medicine physicians, discordant subgroup results being discussed to reach a consensus for positive, negative end equivocal results.

Results

PET results were concordant in 88 out of 92 local, regional and distant findings (Cohen’s kappa 0.929). In particular, results were concordant in all patients concerning local status, bone metastases and distant findings. Lymph-node results were concordant in 19 patients and different in 4 patients. On a per-patient basis results were concordant in 22 of 23 patients (14 positive, 5 negative and 3 equivocal). In only one patient was ACE PET/CT positive for nodal metastases while FCH PET/CT was overall negative; interestingly, the ACE-positive and FCH-negative lymph nodes became positive in a second FCH PET/CT scan performed a few months later.

Conclusion

Overall, ACE and FCH PET/CT showed excellent concordance, on both a per-lesion and a per-patient basis, suggesting that both tracers perform equally for recurrent prostate cancer staging.     

Detection of recurrent prostate cancer with 18F-fluorocholine PET/CT in relation to PSA level at the time of imaging

Purpose

To evaluate fluorine-18 fluorocholine (FCH) PET/CT for the detection of recurrent prostate cancer in relation to prostate-specific antigen (PSA) level.

Methods

FCH PET/CT was performed in 50 patients with rising PSA levels at follow-up of primary treatment of prostate cancer (radical prostatectomy in 28, radiation therapy in 13, and brachytherapy in 9). PET detection rates were determined at various PSA thresholds and examined by receiver operating characteristic analysis.

Results

Findings consistent with recurrent prostate cancer were noted on FCH PET/CT in 31/50 (62?%) patients, with positive findings in 17/18 (94?%), and 11/13 (85?%), 2/7 (29?%), and 1/12 (8?%) patients with PSA >4, >2?C4, >0.5?C2, and ??0.5?ng/mL, respectively. These findings were indicative of local/regional recurrence in 23 cases and systemic recurrence in 8 cases, with only a single route of recurrence (i.e., either hematogenous, lymphatic, or intraprostatic) in 84?% of PET scans with positive findings. Abnormal tumor activity was detected in 88?% of patients with a PSA level of 1.1?ng/mL or higher, and in only 6?% of patients with a PSA level below this threshold value.

Conclusion

FCH PET/CT may serve to identify the route of tumor progression in patients with recurrent prostate cancer; however, the likelihood of tumor detection may be related to the PSA level at the time of imaging.     

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.     

18F-choline PET/CT imaging of RECIST measurable lesions in hormone refractory prostate cancer

Purpose  Apply measurability criteria based on the response evaluation criteria in solid tumors (RECIST) to lesions found on ¹⁸F-choline positron emission tomography (PET)/computerized tomography (CT) in patients with hormone refractory prostate cancer. Methods  Whole-body PET followed by CT or in-line PET/CT using 3.3–4 MBq/kg of ¹⁸F-choline was performed prospectively on 30 patients with prostate cancer, castrate testosterone levels, and rising post-treatment prostate specific antigen (PSA) levels. Lesions demonstrating increased ¹⁸F-choline uptake were classified as measurable or non-measureable based on RECIST. Results  Three patients were known previously to have RECIST measurable lesions, 10 patients had metastatic findings on radionuclide bone scan, and 17 patients had elevated serum PSA level as the only evidence of disease. Lesions demonstrating increased ¹⁸F-choline uptake were found in 28 (93%) patients. Thirty-eight PET/CT lesions from 14 patients were measurable by RECIST. Lymph node maximum standardized uptake value (SUV_max) correlated with lymph node diameter (Pearson r = 0.44, p < 0. 001). RECIST measurable lymph node SUV_max was significantly higher than that of non-measurable nodes (8.1 vs. 3.7, p < 0.0001). Detection of skeletal, prostatic, or RECIST-compatible lesions was more likely with a PSA level greater than 4.0 ng/ml (Fisher exact p = 0.0005). Conclusion  Lesions detected with ¹⁸F-choline PET/CT are frequently measurable by RECIST at baseline. Therefore, it may be feasible to include comparisons to RECIST in evaluations of ¹⁸F-choline as a therapeutic response marker for hormone refractory prostate cancer. The findings and conclusions expressed in this study do not necessarily represent the views of The Queen’s Medical Center.     

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).     

Role of 18F-choline PET/CT in suspicion of relapse following definitive radiotherapy for prostate cancer

Purpose

The aims of the study were (a) to evaluate the diagnostic role, by means of positive detection rate (PDR), of ¹⁸F-choline (CH) positron emission tomography (PET)/CT in patients with prostate cancer treated with radiotherapy, with curative intent, and suspicion of relapse during follow-up, (b) to correlate the PDR with trigger prostate-specific antigen (PSA), (c) to investigate the possible influence of androgen deprivation therapy (ADT) at the time of scan on PDR and (d) to assess distribution of metastatic spread.

Methods

¹⁸F-CH PET/CT exams from 46 consecutive patients (mean age 71.3 years, range 51–84 years) with prostate cancer (mean Gleason score 6.4, range 5–8) previously treated by definitive radiotherapy and with suspicion of relapse with negative or inconclusive conventional imaging were retrospectively evaluated. Of the 46 patients, 12 were treated with brachytherapy and 34 with external beam radiation therapy. Twenty-three patients were under ADT at the time of the examination. Trigger PSA was measured within 1 month before the exam (mean value 6.5 ng/ml, range 1.1–49.4 ng/ml). Patients were subdivided into four groups according to their PSA level: 1.0?<?PSA?≤?2.0 ng/ml (11 patients), 2.0?<?PSA?≤?4.0 ng/ml (16 patients), 4.0?<?PSA?≤?6.0 ng/ml (9 patients) and PSA?>?6.0 ng/ml (10 patients). Correlation between ADT and PDR was investigated as well as between PSA and distribution of metastatic spread.

Results

The overall PDR of ¹⁸F-CH PET/CT was 80.4 % (37/46 patients), increasing with the increase of trigger PSA. PDR of ¹⁸F-CH PET/CT is not influenced by ADT (p?=?0.710) even if PET performed under ADT demonstrated an overall higher PDR (82.6 %). The majority of the patients (59 %, 22/37 patients) showed local relapse only, confined to the prostatic bed; 22 % of the PET/CT-positive patients (8/37 patients) showed distant relapse only (bone localizations in all of them), while the remaining 19 % (7/37 patients) showed both local and distant (lymph node and bone) spread.

Conclusion

¹⁸F-CH PET/CT showed a high overall detection rate (80 %), proportional to the trigger PSA (both for local and distant relapse) not influenced by ADT. ¹⁸F-CH PET/CT is proposed as a first-line imaging procedure in restaging prostate cancer patients primarily treated with radiotherapy.     

<Superscript>11</Superscript>C-acetate PET in the early evaluation of prostate cancer recurrence

Purpose The first aim of the study was to investigate the diagnostic potential of ¹¹C-acetate PET in the early detection of prostate cancer recurrence. A second aim was the evaluation of early and late PET in this context. Methods The study population comprised 32 prostate cancer patients with early evidence of relapse after initial radiotherapy (group A) or radical surgery (group B). The median PSA of group A (n=17) patients was 6 ng/ml (range 2.6–30.2) while that of group B (n=15) was 0.4 ng/ml (range 0.08–4.8). Pelvic-abdominal-thoracic PET was started 2 min after injection of ¹¹C-acetate and evaluated after fusion with CT. Results Group A: Taking a SUV_max≥2 as the cut-off, PET showed local recurrences in 14/17 patients and two equivocal results. Distant disease was observed in six patients and an equivocal result was obtained in one. Endorectal MRI was positive in 12/12 patients. Biopsy confirmed local recurrence in six of six (100%) patients. PET was positive in five of the six patients with biopsy-proven recurrences, the result in the remaining patient being equivocal. Group B: Among the 15 patients, visual interpretation was positive for local recurrences in five patients and equivocal in four. One obturator lymph node was positive. Endorectal MRI was positive in 11/15 patients and equivocal in two. Positional correlation of positive/equivocal results on PET and endorectal MRI was observed in seven of nine patients. PSA decreased significantly after salvage radiotherapy in 8/14 patients, providing strong evidence for local recurrence. PET of the eight patients responding to RT was positive in three and equivocal in two. Conclusion ¹¹C-acetate PET was found to be valuable in the early evaluation of prostate cancer relapse. Optimising scanning time and use of modern PET-CT equipment might allow further improvement.     

Detection of bone metastases in patients with prostate cancer by <Superscript>18</Superscript>F fluorocholine and <Superscript>18</Superscript>F fluoride PET–CT: a comparative study

Purpose  The aim of this prospective study was to compare the potential value of ¹⁸F fluorocholine (FCH) and ¹⁸F fluoride positron emission tomography (PET)–CT scanning for the detection of bony metastases from prostate cancer. Methods  Thirty-eight men (mean age, 69 ± 8 years) with biopsy-proven prostate cancer underwent both imaging modalities within a maximum interval of 2 weeks. Seventeen patients were evaluated preoperatively, and 21 patients were referred for post-operative evaluation of suspected recurrence or progression based on clinical algorithms. The number, sites and morphological patterns of bone lesions on ¹⁸F FCH and ¹⁸F fluoride PET–CT were correlated: Concordant lesions between the two modalities with corresponding changes on CT were considered to be positive for malignancy; discordant lesions were verified by follow-up examinations. The mean follow-up interval was 9.1 months. Results  Overall, 321 lesions were evaluated in this study. In a lesion-based analysis, a relatively close agreement was found between these two imaging modalities for detection of malignant bone lesions (kappa = 0.57), as well as in a patient-based analysis (kappa = 0.76). Sixteen malignant sclerotic lesions with a high density were negative in both ¹⁸F FCH and ¹⁸F fluoride PET–CT [mean Hounsfield unit (HU), 1,148 ± 364]. There was also a significant correlation between tracer intensity by SUV and density of sclerotic lesions by HU both in ¹⁸F FCH PET–CT (r = −0.28, p < 0.006) and ¹⁸F fluoride PET–CT (r = −0.20, p < 0.05). The sensitivity, specificity and accuracy of PET–CT in the detection of bone metastases in prostate cancer was 81%, 93% and 86% for ¹⁸F fluoride, and 74% (p = 0.12), 99% (p = 0.01) and 85% for FCH, respectively. ¹⁸F FCH PET–CT led to a change in the management in two out of 38 patients due to the early detection of bone marrow metastases. ¹⁸F fluoride PET–CT identified more lesions in some patients when compared with ¹⁸F FCH PET–CT but did not change patient management. Conclusion  FCH PET–CT may be superior for the early detection (i.e. bone marrow involvement) of metastatic bone disease. In patients with FCH-negative suspicious sclerotic lesions, a second bone-seeking agent (e.g. ¹⁸F fluoride) is recommended. ¹⁸F fluoride PET–CT demonstrated a higher sensitivity than ¹⁸F FCH PET–CT, but the difference was not statistically significant. Furthermore, ¹⁸F fluoride PET could be also negative in highly dense sclerotic lesions, which presumably reflects the effect of treatment. It will be important to clarify in future studies whether these lesions are clinically relevant when compared with metabolically active bone metastases.     

Diagnostic performance of <Superscript>18</Superscript>F-PSMA-1007 PET/CT in patients with biochemical recurrent prostate cancer

Purpose

The introduction of ligands targeting prostate-specific membrane antigen (PSMA), especially ⁶⁸Ga-PSMA-11, has changed the management of patients with prostate cancer (PCa). ¹⁸F-Labelled ligands can be produced in larger amounts and therefore can improve availability for a larger group of patients. The aim of this study was to evaluate the diagnostic performance of the recently introduced ¹⁸F-PSMA-1007 in patients with recurrent PCa.

Methods

This retrospective analysis included 100 consecutive patients with biochemical relapse (mean age 68.75?±?7.6 years) referred for PSMA PET/CT. Whole-body PET/CT imaging (from the lower limbs to the skull) was performed in all patients 120 min after injection of 338?±?44.31 MBq ¹⁸F-PSMA-1007. Prostatectomy, radiation beam therapy of the prostate bed and androgen-deprivation therapy had been performed in 92%, 45% and 27% of the patients, respectively. Radiation beam therapy of the prostate bed had been performed in addition to surgery in 38 patients (38%) and 10 patients (10%) had received all three therapy modalities. The probability of a ¹⁸F-PSMA-1007 PET/CT scan suggestive of pathology was compared with the Gleason score (GS) and PSA level.

Results

Of the 100 patients, 95 (95%) showed at least one pathological finding on ¹⁸F-PSMA-1007 PET/CT. The overall median PSA level was 1.34 ng/ml (range 0,04–41.3 ng/ml). The rates of pathological scans were 86%, 89%, 100% and 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and?>?2.0 ng/ml, respectively. The median GS was 7 (range 5–10). The majority of patients (70) with a GS available had a score in the range 7–9. The rate of pathological scans in these patients was 93% (65/70). The median SUV_max values of the pathological findings were 10.25, 14.32, 13.16 and 28.87 in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/ml, respectively. The median SUV_max in patients with a PSA level of >2.0 ng/ml was significantly higher than in all other PSA groups.

Conclusion

¹⁸F-PSMA-1007 PET/CT can detect recurrent PCa in a high percentage of patients with biochemical relapse. The probability of a pathological ¹⁸F-PSMA-1007 PET/CT scan seems to be high even in patients with a low PSA level ≤0.5 ng/ml, and this may have a significant impact on the management of this relevant group of patients.