<Superscript>18</Superscript>F-fluorodeoxyglucose positron emission tomography in uterine carcinosarcoma

Purpose Uterine carcinosarcomas clinically confined to the uterus usually harbor occult metastases. We conducted a pilot study to evaluate the value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in uterine carcinosarcoma. Methods Patients with histologically confirmed uterine carcinosarcoma were enrolled. Abdominal and pelvic magnetic resonance imaging (MRI)/whole-body computed tomography (CT) scan, and whole-body ¹⁸F-FDG PET or PET/CT were undertaken for primary staging, evaluating response, and restaging/post-therapy surveillance. The clinical impact of ¹⁸F-FDG PET was determined on a scan basis. Results A total of 19 patients were recruited and 31 ¹⁸F-FDG PET scans (including 8 scans performed on a PET/CT scanner) were performed. Positive impacts of scans were found in 36.8% (7/19) for primary staging, 66.7% (2/3) for monitoring response, and 11.1% (1/9) for restaging/post-therapy surveillance. PET excluded falsely inoperable disease defined by MRI in two patients. Aggressive treatment applying to three patients with PET-defined resectable stage IVB disease seemed futile. Two patients died of disease shortly after salvage therapy restaged by PET. With PET monitoring, one stage IVB patient treated by targeted therapy only was alive with good performance. Using PET did not lead to improvement of overall survival of this series compared with the historical control (n = 35) (P = 0.779). Conclusions The preliminary results suggest that ¹⁸F-FDG PET is beneficial in excluding falsely inoperable disease for curative therapy and in making a decision on palliation for better quality of life instead of aggressive treatment under the guidance of PET. PET seems to have limited value in post-therapy surveillance or restaging after failure.     

<Superscript>18</Superscript>F-FDG PET in small-cell cervical cancer: a prospective study with long-term follow-up

Purpose

Small-cell cervical cancer (SCCC) is rare and prone to metastasize. We conducted a prospective study to evaluate the role of ¹⁸F-FDG PET in the management of this aggressive malignancy.

Methods

Patients with untreated primary, histologically confirmed SCCC were enrolled. ¹⁸F-FDG PET (or PET/CT) was performed immediately after MRI or CT, for primary staging, monitoring response to treatment or restaging when there was suspicion of recurrence. The clinical impact of PET was determined on a scan basis.

Results

A total of 25 patients were recruited and 43 PET scans were performed. The PET images were obtained for primary staging (25 patients), monitoring response (10 patients) and restaging when there was suspicion of recurrence (8 patients). The median follow-up time in event-free patients was 109.3 months (range 97.5 – 157.7 months). A positive impact of PET was found in 8 (18.6 %) of the 43 scans, which included detection of additional regions of distal lymph node (LN) metastasis (one primary staging scan, two restaging scans), bone metastasis (two primary staging scans, one monitoring response scan), and exclusion of false-positive lesions on MRI (one primary staging scan, one restaging scan). On the other hand, one negative impact was recorded as one false-positive lesion on a restaging PET scan. One positive impact was noted for monitoring response (bone metastasis). The impact of three scans was indeterminate. The positive impact of down-staging in avoiding overtreatment but finding additional distal LN (except one on restaging) or bone metastases had no beneficial effect on long-term survival.

Conclusion

The results of this preliminary study suggest that PET is useful in the management of SCCC. PET could have more value in detecting occult metastases if future novel therapies are able to offer better control of extensive SCCC.

     

Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in <Superscript>68</Superscript>Ga-DOTATOC PET/CT

Purpose  In clinical routine somatostatin analogue positron emission tomography/computed tomography (PET/CT) such as ⁶⁸Ga-DOTA-Tyr-octreotide (DOTATOC)-PET/CT could substitute conventional ¹¹¹In-Octreotide scintigraphy. Immunohistochemistry (IHC) for somatostatin receptor 2 (SSTR2) might be a tool to predict positivity of ⁶⁸Ga-DOTATOC in patients where initial staging was not performed, e.g., in incidental findings. We therefore compared a score of SSTR2-IHC with the in vivo standard uptake value (SUV) of preoperative or prebiopsy ⁶⁸Ga-DOTATOC PET/CT. Materials and methods  In 18 patients, ⁶⁸Ga-DOTATOC PET/CT scans were quantified with SUV calculations and correlated to a cell membrane-based SSTR2-IHC score (ranging from 0 to 3). Results  Negative IHC scores were consistent with SUV values below 10. Furthermore, all score 2 and 3 specimens corresponded with high SUV values (above 15). Conclusion  SSTR2-IHC scores correlated well with SUV values and we propose to use SSTR2 immunohistochemistry in patients missing a preoperative PET scan to indicate ⁶⁸Ga-DOTATOC-PET/CT as method for restaging and follow-up in individual patients.     

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.     

[18F]fluorocholine PET/CT imaging for the detection of recurrent prostate cancer at PSA relapse: experience in 100 consecutive patients

Purpose We evaluated the potential of PET/CT and [¹⁸F]fluoromethylcholine (FCH) in the assessment of suspected recurrence of prostate cancer after treatment. Methods One hundred consecutive prostate cancer patients with a persistent increase in serum PSA (>0.1 ng/ml) after radical prostatectomy (58 cases), radiotherapy (21 cases) or hormonal therapy alone (21 cases) were investigated. After injection of 3.7–4.07 MBq/kg of FCH, both early (at <15 min) and delayed (at >60 min) PET/CT scans were performed in 43 patients, delayed PET/CT scans in 53 patients and early PET/CT scans in four patients. Results Of the 100 patients, 54 (PSA 0.22–511.79 ng/ml) showed positive FCH PET/CT scans. Thirty-seven patients had bone and/or abdominal lymph node uptake, while 17 showed pelvic activity. Malignant disease was confirmed in all but one. Delayed SUV_max of bone metastases was significantly higher (p<0.0001 by paired t test) than that measured at <15 min, whereas no differences were observed between early and delayed SUVs of malignant lymph nodes or pelvic disease. Forty-six patients (PSA 0.12–14.3 ng/ml) showed negative FCH PET/CT scans. Of the negative PET/CT scans, 89% were obtained in patients with serum PSA <4 ng/ml and 87% in patients with a Gleason score <8. In none of these cases could recurrent tumour be proven clinically during a follow-up of 6 months. Conclusion FCH 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, FCH PET/CT helps to exclude distant metastases when salvage local treatment is intended.     

Prospective head-to-head comparison of <Superscript>11</Superscript>C-choline-PET/MR and <Superscript>11</Superscript>C-choline-PET/CT for restaging of biochemical recurrent prostate cancer

Purpose

Whole-body integrated ¹¹C-choline PET/MR might provide advantages compared to ¹¹C-choline PET/CT for restaging of prostate cancer (PC) due to the high soft-tissue contrast and the use of multiparametric MRI, especially for detection of local recurrence and bone metastases.

Materials and methods

Ninety-four patients with recurrent PC underwent a single-injection/dual-imaging protocol with contrast-enhanced PET/CT followed by fully diagnostic PET/MR. Imaging datasets were read separately by two reader teams (team 1 and 2) assessing the presence of local recurrence, lymph node and bone metastases in predefined regions using a five-point scale. Detection rates were calculated. The diagnostic performance of PET/CT vs. PET/MR was compared using ROC analysis. Inter-observer and inter-modality variability, radiation exposure, and mean imaging time were evaluated. Clinical follow-up, imaging, and/or histopathology served as standard of reference (SOR).

Results

Seventy-five patients qualified for the final image analysis. A total of 188 regions were regarded as positive: local recurrence in 37 patients, 87 regions with lymph node metastases, and 64 regions with bone metastases. Mean detection rate between both readers teams for PET/MR was 84.7% compared to 77.3% for PET/CT (p > 0.05). Local recurrence was identified significantly more often in PET/MR compared to PET/CT by team 1. Lymph node and bone metastases were identified significantly more often in PET/CT compared to PET/MR by both teams. However, this difference was not present in the subgroup of patients with PSA values ≤2 ng/ml.Inter-modality and inter-observer agreement (K > 0.6) was moderate to substantial for nearly all categories. Mean reduction of radiation exposure for PET/MR compared to PET/CT was 79.7% (range, 72.6–86.2%). Mean imaging time for PET/CT was substantially lower (18.4 ± 0.7 min) compared to PET/MR (50.4 ± 7.9 min).

Conclusions

¹¹C-choline PET/MR is a robust imaging modality for restaging biochemical recurrent PC and interpretations between different readers are consistent. It provides a higher diagnostic value for detecting local recurrence compared to PET/CT with the advantage of substantial dose reduction. Drawbacks of PET/MR are a substantially longer imaging time and a slight inferiority in detecting bone and lymph node metastases in patients with PSA values >2 ng/ml. Thus, we suggest the use of ¹¹C-choline PET/MR especially for patients with low (≤2 ng/ml) PSA values, whereas PET/CT is preferable in the subgroup with higher PSA values.

     

Tumour assessment in advanced melanoma: value of FDG-PET/CT in patients with elevated serum S-100B

Purpose To evaluate the usefulness of PET/CT in melanoma patients with an elevated serum S-100B tumour marker level. Methods Out of 165 consecutive high-risk melanoma patients referred for PET/CT imaging, 47 had elevated (>0.2 μg/l) S-100B serum levels and a contemporaneous ¹⁸F-FDG PET/CT scan. PET/CT scans were evaluated for the presence of metastases. To produce a composite reference standard, we used cytological, histological, MRI and PET/CT follow-up findings as well as clinical and S-100B follow-up. Results Among the 47 patients with increased S-100B levels, PET/CT correctly identified metastases in 38 (30 distant metastases and eight lymph node metastases). In one patient with cervical lymph node metastases, PET/CT was negative. Eight patients had no metastases and PET/CT correctly excluded metastases in all of them. Overall sensitivity for metastases was 97% (38/39), specificity 100% (8/8) and accuracy 98% (46/47). S-100B was significantly higher in patients with distant metastases (mean 1.93 μg/l, range 0.3–14.3 μg/l) than in patients with lymph node metastases (mean 0.49 μg/l, range 0.3–1.6 μg/l, p = 0.003) or patients without metastases (mean 0.625 μg/l, range 0.3–2.6 μg/l, p = 0.007). However, 6 of 14 patients with a tumour marker level of 0.3 μg/l had no metastases. Conclusion In melanoma patients with elevated S-100B tumour marker levels, FDG-PET/CT accurately identifies lymph node or distant metastases and reliably excludes metastases. Because of the significant number of false positive S-100B tumour marker determinations (17%), we recommend repetition of tumour marker measurements if elevated S-100B levels occur before extensive imaging is used.     

<Superscript>11</Superscript>C-Choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series

Purpose

To evaluate ¹¹C-choline PET/CT as a diagnostic tool for restaging prostate cancer (PCa), in a large, homogeneous and clinically relevant population of patients with biochemical recurrence (BCR) of PCa after primary therapy. The secondary aim was to assess the best timing for performing ¹¹C-choline PET/CT during BCR.

Methods

We retrospectively analysed 9,632 ¹¹C-choline PET/CT scans performed in our institution for restaging PCa from January 2007 to June 2015. The inclusion criteria were: (1) proven PCa radically treated with radical prostatectomy (RP) or with primary external beam radiotherapy (EBRT); (2) PSA serum values available; (3) proven BCR (PSA >0.2 ng/mL after RP or PSA >2 ng/mL above the nadir after primary EBRT with rising PSA levels). Finally, 3,203 patients with recurrent PCa matching all the inclusion criteria were retrospectively enrolled and 4,426 scans were analysed.

Results

Overall, 52.8 % of the ¹¹C-choline PET/CT scans (2,337/4,426) and 54.8 % of the patients (1,755/3,203) were positive. In 29.4 % of the scans, at least one distant finding was observed. The mean and median PSA values were, respectively, 4.9 and 2.1 ng/mL at the time of the scan (range 0.2 – 50 ng/mL). In our series, 995 scans were performed in patients with PSA levels between 1 and 2 ng/mL. In this subpopulation the positivity rate in the 995 scans was 44.7 %, with an incidence of distant findings of 19.2 % and an incidence of oligometastatic disease (one to three lesions) of 37.7 %. The absolute PSA value at the time of the scan and ongoing androgen deprivation therapy were associated with an increased probability of a positive ¹¹C-choline PET/CT scan (p?<?0.0001). In the ROC analysis, a PSA value of 1.16 ng/mL was the optimal cut-off value. In patients with a PSA value <1.16 ng/mL, 26.8 % of 1,426 ¹¹C-choline PET/CT scans were positive, with oligometastatic disease in 84.7 % of positive scans.

Conclusion

In a large cohort of patients, the feasibility of ¹¹C-choline PET/CT for detecting the sites of metastatic disease in PCa patients with BCR was confirmed. The PSA level was the main predictor of a positive scan with 1.16 ng/mL as the optimal cut-off value. In the majority of positive scans oligometastatic disease, potentially treatable with salvage therapies, was observed.

     

Nonionic intravenous contrast agent does not cause clinically significant artifacts to <Superscript>18</Superscript>F-FDG PET/CT in patients with lung cancer

Objective This study was performed to evaluate the effects of intravenous (i.v.) contrast agent on semi-quantitative values and lymph node (LN) staging of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with lung cancer. Methods Thirty-five patients with lung cancer were prospectively included. Whole-body PET and nonenhanced CT images were acquired 60 min following the i.v. injection of 370 MBq ¹⁸F-FDG and subsequently, enhanced-CT images were acquired with the i.v. administration of 400 mg iodinated contrast agent without positional change. PET images were reconstructed with both nonenhanced and enhanced CTs, and the maximum and average standardized uptake values (SUV_max and SUV_ave) calculated from lung masses, LNs, metastatic lesions, and normal structures were compared. To evaluate the effects of the i.v. contrast agent on LN staging, we compared the LN status on the basis of SUVs (cut-offs; SUV_max = 3.5, SUV_ave = 3.0). Results The mean differences of SUV_max in normal structures between enhanced and nonenhanced PET/CT were 15.23% ± 13.19% for contralateral lung, 8.53% ± 6.11% for aorta, 5.85% ± 4.99% for liver, 5.47% ± 6.81% for muscle, and 2.81% ± 3.05% for bone marrow, and those of SUV_ave were 10.17% ± 9.00%, 10.51% ± 7.89%, 4.95% ± 3.89%, 5.66% ± 9.12%, and 2.49% ± 2.50%, respectively. The mean differences of SUV_max between enhanced and nonenhanced PET/CT were 5.89% ± 3.92% for lung lesions (n = 41), 6.27% ± 3.79% for LNs (n = 76), and 3.55% ± 3.38% for metastatic lesions (n = 35), and those of SUV_ave were 3.22% ± 3.01%, 2.86% ± 1.71%, and 2.33% ± 3.95%, respectively. Although one LN status changed from benign to malignant because of contrast-related artifact, there was no up- or down-staging in any of the patients after contrast enhancement. Conclusions An i.v. contrast agent may be used in PET/CT without producing any clinically significant artifact.     

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.     

Comparison of whole-body <Superscript>18</Superscript>F-FDG PET, <Superscript>99m</Superscript>Tc-MIBI SPET,and post-therapeutic <Superscript>131</Superscript>I-Na scintigraphy in the detection of metastatic thyroid cancer

The usefulness of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid cancer (DTC) has been demonstrated by many investigators, but in only a small number of studies have FDG-PET images been compared with those obtained using other non-iodine tumour-seeking radiopharmaceuticals. In most of the studies, planar imaging was performed for comparison using thallium-201 chloride or technetium-99m 2-methoxyisobutylisonitrile (^99mTc-MIBI). Furthermore, FDG-PET studies were not always performed in the hypothyroid state with increased levels of thyroid stimulating hormone (TSH), which are known to increase FDG uptake by DTC. The aim of this study was to compare the ability of FDG-PET to detect metastatic DTC with that of ^99mTc-MIBI whole-body single-photon emission tomography (SPET) and post-therapeutic iodine-131 scintigraphy, evaluated under TSH stimulation. Nineteen patients (8 men, 11 women; age range, 38–72 years, mean 60 years; 17 thyroidectomised and 2 inoperable patients following ¹³¹I ablation of the remaining thyroid tissue; 16 papillary and 3 follicular carcinomas) with metastatic DTC underwent FDG-PET whole-body scan (WBS) and ^99mTc-MIBI SPET WBS at an interval of less than 1 week, followed by ¹³¹I therapy. The SPET images were reconstructed using the maximum likelihood expectation maximisation (ML-EM) method. All patients were hypothyroid at the time of each scan. ¹³¹I WBS was performed 3–5 days after oral administration of the therapeutic dose. A total of 32 lesions [10 lymph node (LN), 15 lung, 6 bone, 1 muscle] were diagnosed as metastases, as confirmed by histopathology and/or other imaging modalities (X-ray, US, CT, MRI, bone, ²⁰¹Tl and ¹³¹I scans). FDG-PET, ^99mTc-MIBI SPET and post-therapeutic ¹³¹I scintigraphy respectively revealed a total of 26 (81.3%), 20 (62.5%) and 22 (68.8%) lesions. These techniques respectively demonstrated nine (90.0%), eight (80.0%) and six (60.0%) LN metastases, and eleven (73.3%), seven (46.7%) and ten (66.7%) lung metastases. They each demonstrated five of the six bone metastases (83.3%). FDG-PET and ^99mTc-MIBI SPET were positive in 17 (78.3%) and 14 (63.6%) of the 22 ¹³¹I-positive lesions, respectively, and also in nine (90.0%) and six (60.0%) of the ten ¹³¹I-negative lesions, respectively. Three of the five ¹³¹I-positive and FDG-PET-negative lesions were miliary type lung metastases with a maximal nodular diameter of less than 10 mm. Comparison of FDG-PET with ^99mTc-MIBI SPET revealed concordant results in 24 lesions, and discordant results in eight lesions (seven with positive FDG-PET alone and one with positive ^99mTc-MIBI SPET alone). In conclusion: (a) even using whole-body SPET, FDG PET is superior to ^99mTc-MIBI in terms of ability to detect metastases of DTC; (b) the higher sensitivity of FDG-PET compared with the previous studies could partly be due to increased serum TSH.     

<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.     

<Superscript>18</Superscript>F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide

Purpose

We investigated the role of ¹⁸F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide.

Methods

The study group comprised 36 patients with a median age of 72 years (range 48–90 years) who were treated with enzalutamide 160 mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3–6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS).

Results

At a median follow-up of 24.2 months (range 1.8–27.3 months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50 % was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3 months in advance of CT in 12 of 18 patients (66 %) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2 months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (p?=?0.0005 and p?=?0.029, respectively), whereas decrease in PSA level alone was predictive of OS (p?=?0.007).

Conclusion

This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response to enzalutamide in mCRPC patients.

     

Intraindividual comparison of <Superscript>68</Superscript>Ga-DOTA-TATE and <Superscript>18</Superscript>F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

Aim  To compare the diagnostic impact of ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). Methods  PET/CT using both ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Results  Patient-based sensitivities were 96% for ⁶⁸Ga-DOTA-TATE PET and 56% for ¹⁸F-DOPA PET. ⁶⁸Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by ¹⁸F-DOPA PET. Overall, ⁶⁸Ga-DOTA-TATE was superior to ¹⁸F-DOPA in 13 patients (two patients showed fewer positive tumour regions with ¹⁸F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of ¹⁸F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive ¹⁸F-DOPA uptake. In patients positive for ¹⁸F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). Conclusion  In this study ⁶⁸Ga-DOTA-TATE PET proved clearly superior to ¹⁸F-DOPA PET for detection and staging of NET. ¹⁸F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that ¹⁸F-DOPA PET should be employed in patients with NET with negative ⁶⁸Ga-DOTA-TATE PET and elevated plasma serotonin.     

Correlation of <Superscript>18</Superscript>F-FLT and <Superscript>18</Superscript>F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer

Purpose The nucleoside analogue 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) has recently been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively evaluated whether FLT uptake reflects proliferative activity as indicated by the Ki-67 index in non-small cell lung cancer (NSCLC), in comparison with 2-deoxy-2-¹⁸F-fluoro-D-glucose (FDG). Methods A total of 18 patients with newly diagnosed NSCLC were examined with both FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. Tumour lesions were identified as areas of focally increased uptake, exceeding background uptake in the lungs. For semi-quantitative analysis, the maximum standardised uptake value (SUV) was calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with SUVs. Results The sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%, respectively. Four of the five false-negative FLT PET findings occurred in bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67 index (r = 0.77; p < 0.0002) and for FDG SUV (r = 0.81; p < 0.0001). Conclusion The results of this preliminary study suggest that, compared with FDG, FLT may be less sensitive for primary staging in patients with NSCLC. Although FLT uptake correlated significantly with proliferative activity in NSCLC, the correlation was not better than that for FDG uptake.     

Combined metabolic and morphologic imaging in thyroid carcinoma patients with elevated serum thyroglobulin and negative cervical ultrasonography: role of <Superscript>124</Superscript>I-PET/CT and FDG-PET

Purpose This study sought to compare iodine-124 positron emission tomography/computed tomography (¹²⁴I-PET/CT) and 2-[¹⁸F]fluoro-2-deoxy-d-glucose- (FDG-) PET in the detection of recurrent differentiated thyroid carcinoma (DTC) lesions in patients with increasing serum thyroglobulin (Tg), Tg-antibodies, or both, but without pathological cervical ultrasonography. We assessed the lesion detection accuracy of ¹²⁴I-PET alone, CT alone, ¹²⁴I-PET/CT, FDG-PET, and all these modalities combined. Material and methods The study included 21 patients (9 follicular, 12 papillary DTC) who had been rendered disease-free by thyroidectomy and radioiodine treatment (RIT) and followed up for 21–275 months after the last RIT. In all patients, FDG-PET was performed first. Within 1 week, ¹²⁴I-PET/CT was performed 24 h after oral administration of 43 ± 11 MBq ¹²⁴I. Imaging results were correlated with further clinical follow-up with (n = 12) or without (n = 9) post-study histology as the reference standard. Results The sensitivities for DTC lesion detection were: ¹²⁴I-PET, 49%; CT, 67%; ¹²⁴I-PET/CT, 80%; FDG-PET, 70%; and all modalities combined, 91%. For local recurrences (distant metastases), the sensitivities were: ¹²⁴I-PET, 60% (45%); CT, 20% (84%); and FDG-PET, 65% (71%). One-third of lesions demonstrated pathological tracer uptake with both ¹²⁴I- and FDG-PET, while two-thirds were positive with only one of these modalities. Conclusion Used together, ¹²⁴I-PET and CT allow localization of foci of highly specific ¹²⁴I uptake as well as non-iodine-avid lesions. The combination of ¹²⁴I-PET/CT and FDG-PET improves restaging in recurrent DTC by enabling detection on whole-body scans of local recurrence or metastases that are often not found if only one of the methods or other imaging modalities are applied.     

<Superscript>68</Superscript>Ga-PSMA PET/CT in patients with recurrent prostate cancer after radical treatment: prospective results in 314 patients

Purpose

We studied the usefulness of ⁶⁸Ga-prostate-specific membrane antigen (PSMA) PET/CT for detecting relapse in a prospective series of patients with biochemical recurrence (BCR) of prostate cancer (PCa) after radical treatment.

Methods

Patients with BCR of PCa after radical surgery and/or radiotherapy with or without androgen-deprivation therapy were included in the study. ⁶⁸Ga-PSMA PET/CT scans performed from the top of the head to the mid-thigh 60 min after intravenous injection of 150?±?50 MBq of ⁶⁸Ga-PSMA were interpreted by two nuclear medicine physicians. The results were correlated with prostate-specific antigen (PSA) levels at the time of the scan (PSApet), PSA doubling time, Gleason score, tumour stage, postsurgery tumour residue, time from primary therapy to BCR, and patient age. When available, ⁶⁸Ga-PSMA PET/CT scans were compared with negative ¹⁸F-choline PET/CT scans routinely performed up to 1 month previously.

Results

From November 2015 to October 2017, 314 PCa patients with BCR were evaluated. Their median age was 70 years (range 44–92 years) and their median PSApet was 0.83 ng/ml (range 0.003–80.0 ng/ml). ⁶⁸Ga-PSMA PET/CT was positive (one or more suspected PCa lesions detected) in 197 patients (62.7%). Lesions limited to the pelvis, i.e. the prostate/prostate bed and/or pelvic lymph nodes (LNs), were detected in 117 patients (59.4%). At least one distant lesion (LNs, bone, other organs, separately or combined with local lesions) was detected in 80 patients (40.6%). PSApet was higher in PET-positive than in PET-negative patients (P?<?0.0001). Of 88 patients negative on choline PET/CT scans, 59 (67%) were positive on ⁶⁸Ga-PSMA PET/CT.

Conclusion

We confirmed the value of ⁶⁸Ga-PSMA PET/CT in restaging PCa patients with BCR, highlighting its superior performance and safety compared with choline PET/CT. Higher PSApet was associated with a higher relapse detection rate.

     

Extent of disease in recurrent prostate cancer determined by [<Superscript>68</Superscript>Ga]PSMA-HBED-CC PET/CT in relation to PSA levels,PSA doubling time and Gleason score

Purpose

To examine the relationship between the extent of disease determined by [⁶⁸Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score.

Methods

We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for [⁶⁸Ga]PSMA-HBED-CC PET/CT.

Results

PET/CT was positive in 44 %, 79 % and 89 % of patients with PSA levels of ≤1, 1 – 2 and ≥2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours (p?<?0.001), and extrapelvic lymph node (p?=?0.037) and bone metastases (p?=?0.013). A shorter PSAdt was significantly associated with pelvic lymph node (p?=?0.026), extrapelvic lymph node (p?=?0.001), bone (p?<?0.001) and visceral (p?=?0.041) metastases. A high Gleason score was associated with more frequent pelvic lymph node metastases (p?=?0.039). In multivariate analysis, both PSA and PSAdt were independent determinants of scan positivity and of extrapelvic lymph node metastases. PSAdt was the only independent marker of bone metastases (p?=?0.001). Of 20 patients with a PSAdt <6 months and a PSA ≥2 ng/ml, 19 (95 %) had a positive scan and 12 (60 %) had M1a disease. Of 14 patients with PSA <1 ng/ml and PSAdt >6 months, only 5 (36 %) had a positive scan and 1 (7 %) had M1a disease.

Conclusion

[⁶⁸Ga]PSMA-HBED-CC PET/CT will identify PCA lesions even in patients with very low PSA levels. Higher PSA levels and shorter PSAdt are independently associated with scan positivity and extrapelvic metastases, and can be used for patient selection for [⁶⁸Ga]PSMA-HBED-CC PET/CT.

     

<Superscript>68</Superscript>Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer

Purpose

The aims of this retrospective analysis were to compare ⁶⁸Ga-PSMA PET findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative and quantitative ⁶⁸Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases.

Methods

In total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with ⁶⁸Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually), semiquantitatively (SUV), and quantitatively based on a two-tissue compartment model and a noncompartmental approach leading to the extraction of the fractal dimension. Differences were considered significant for p values <0.05.

Results

In total, 168 ⁶⁸Ga-PSMA-positive and 113 CT-positive skeletal lesions were detected in 37 patients (8 with primary PC, 29 with biochemical recurrence). Of these 168 lesions, 103 were both ⁶⁸Ga-PSMA PET-positive and CT-positive, 65 were only ⁶⁸Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that there were significantly more ⁶⁸Ga-PSMA PET-positive lesions than CT-positive lesions. Association analysis showed that PSA plasma levels were significantly correlated with several ⁶⁸Ga-PSMA-11-associated parameters in bone metastases, including the degree of tracer uptake (SUV_average and SUV_max), its transport rate from plasma to the interstitial/intracellular compartment (K₁), its rate of binding to the PSMA receptor and its internalization (k₃), its influx rate (K_i), and its distribution heterogeneity.

Conclusion

⁶⁸Ga-PSMA PET/CT is a useful diagnostic tool in the detection of bone metastases in PC. ⁶⁸Ga-PSMA PET visualizes more bone metastases than low-dose CT. PSA plasma levels are significantly correlated with several ⁶⁸Ga-PSMA PET parameters.

     

The accuracy of <Superscript>68</Superscript>Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer

Purpose

To assess the diagnostic accuracy of ⁶⁸Ga-PSMA PET in predicting lymph node (LN) metastases in primary N staging in high-risk and very high-risk nonmetastatic prostate cancer in comparison with morphological imaging.

Methods

This was a multicentre trial of the Society of Urologic Oncology in Turkey in conjunction with the Nuclear Medicine Department of Cerrahpasa School of Medicine, Istanbul University. Patients were accrued from eight centres. Patients with high-risk and very high-risk disease scheduled to undergo surgical treatment with extended LN dissection between July 2014 and October 2015 were included. Either MRI or CT was used for morphological imaging. PSMA PET/CT was performed and evaluated at a single centre. Sensitivity, specificity and accuracy were calculated for the detection of lymphatic metastases by PSMA PET/CT and morphological imaging. Kappa values were calculated to evaluate the correlation between the numbers of LN metastases detected by PSMA PET/CT and by histopathology.

Results

Data on 51 eligible patients are presented. The sensitivity, specificity and accuracy of PSMA PET in detecting LN metastases in the primary setting were 53%, 86% and 76%, and increased to 67%, 88% and 81% in the subgroup with of patients with ≥15 LN removed. Kappa values for the correlation between imaging and pathology were 0.41 for PSMA PET and 0.18 for morphological imaging.

Conclusions

PSMA PET/CT is superior to morphological imaging for the detection of metastatic LNs in patients with primary prostate cancer. Surgical dissection remains the gold standard for precise lymphatic staging.