<Superscript>18</Superscript>F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma

Purpose

To evaluate the performance of ¹⁸F-l-dihydroxyphenylalanine (¹⁸F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data.

Methods

We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone ¹⁸F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality.

Results

¹⁸F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of ¹⁸F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 – 1,960 pg/mL) and 259 pg/mL (range 33 – 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation.

Conclusion

¹⁸F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by ¹⁸F-DOPA PET/CT.

     

Diagnostic utility of PET/CT with <Superscript>18</Superscript>F-DOPA and <Superscript>18</Superscript>F-FDG in persistent or recurrent medullary thyroid carcinoma: the importance of calcitonin and carcinoembryonic antigen cutoff

Purpose

This study sought to evaluate and compare the utility of 18-F-fluorodihydroxyphenylalanine (¹⁸F-DOPA) and 18-F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) for identification of lesions in patients with recurrent medullary thyroid carcinoma (MTC). In addition, we analyzed the correlation between the calcitonin (Ct), carcinoembryonic antigen (CEA) levels, each doubling time (DT), and PET positivity. We evaluated the reliability of the 150 pg/mL Ct cutoff set by the American Thyroid Association guidelines for further imaging (including ¹⁸F-DOPA PET/CT).

Methods

We prospectively recruited 18 patients with recurrent MTC, identified by elevation of Ct or CEA. Each patient underwent a ¹⁸F-FDG PET/CT and a ¹⁸F-DOPA PET/CT.

Results

Abnormal uptakes were detected with ¹⁸F-DOPA (n=12) and ¹⁸F-FDG (n=9), (sensitivity of 66.7% vs. 50%; p<0.01). Twenty-eight lesions were detected with ¹⁸F-DOPA vs. 16 lesions with ¹⁸F-FDG (1.56±1.5 vs. 0.89±1.18 lesions per patient; p=0.01). None of our patients showed additional lesions with ¹⁸F-FDG in comparison to ¹⁸F-DOPA. Patient-based detection rate increased significantly with Ct levels ≥150 pg/mL vs. Ct<150 pg/mL for both ¹⁸F-DOPA (sensitivity 90.9% vs. 28.6%; p=0.013) and ¹⁸F-FDG PET/CT (sensitivity 72.7% vs. 14.3%; p=0.025). Using a CEA cutoff of ≥5 ng/mL, detection rates of ¹⁸F-DOPA and ¹⁸F-FDG PET/CT were 81.1% and 72.7%, respectively. No correlation between Ct-DT or CEA-DT and PET positivity was found. Histological confirmation was obtained in eight patients.

Conclusions

¹⁸F-DOPA PET/CT appears to be superior to ¹⁸F-FDG PET/CT in detecting and locating lesions in patients with recurrent MTC. This technique tends to be especially useful in patients with negative results in other imaging modalities and Ct≥150 pg/mL or CEA≥5 ng/mL.

     

Compared to <Superscript>123</Superscript>I-MIBG SPECT/CT, <Superscript>18</Superscript>F-DOPA PET/CT provides accurate tumor extent in patients with extra-adrenal paraganglioma

Aim

The aim of this study was to compare the accuracy of ¹²³I-MIBG SPECT/CT with that of ¹⁸F-DOPA PET/CT for staging extra-adrenal paragangliomas (PGLs) using both functional and anatomical images (i.e., combined cross-sectional imaging) as the reference standards.

Methods

Three men and seven women (age range 26–73 years) with anatomical and/or histologically proven disease were included in this study. Three patients had either metastatic head-and-neck paragangliomas (HNPGLs) or multifocal PGL, and seven patients had nonmetastatic disease. Comparative evaluation included morphological imaging with CT, functional imaging with ¹⁸F-DOPA PET, and ¹²³I-MIBG imaging including SPECT/CT. Imaging results were analyzed on a per-patient and per-lesion basis.

Results

On a per-patient basis, ¹⁸F-DOPA PET’s detection rate for both nonmetastatic and metastatic/multifocal disease was 100%, whereas that of planar ¹²³I-MIBG imaging alone was 10.0% and that of ¹²³I-MIBG SPECT/CT was 20.0%. Overall, on a per-lesion basis, ¹⁸F-DOPA PET showed a sensitivity of 69.2% (McNemar p?<?0.001) compared with anatomical imaging. Sensitivity of planar ¹²³I-MIBG scintigraphy was 5.6%, and that of SPECT/CT was 11.1% (McNemar p?<?0.0001). Overall, ¹⁸F-DOPA PET identified 18 lesions, and anatomical imaging identified 26 lesions; planar ¹²³IMIBG imaging identified only 1 lesion, and SPECT/CT, 2 lesions.

Conclusion

¹⁸F-DOPA PET is more sensitive than is ¹²³I-MIBG imaging, including SPECT/CT, for staging HNPGL. Combined functional and anatomical imaging (PET/CT) is indicated to exclude metastatic disease in extra-adrenal PGL.

     

Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid

Introduction

Medullary thyroid carcinoma (MTC) is a malignancy accounting for about 5–8% of thyroid cancers. Serum calcitonin and carcinoembryonic antigen (CEA) levels are widely used to monitor disease progression. However, prognostic factors able to predict outcomes are highly desirable. We, therefore, aimed to assess the prognostic role of ¹⁸F-DOPA PET/CT in patients with recurrent MTC.

Materials and methods

60 patients (mean age 64?±?13 years, range 44–82) with recurrent MTC were eligible from a multicenter database. All patients underwent a restaging ¹⁸F-DOPA PET/CT, performed at least 6 months after surgery. CEA/calcitonin levels, local recurrences, nodal involvement and metastases at PET/CT were recorded. SUVmax, SUVmean (also normalized to mediastinal uptake) and metabolic tumor volume were automatically calculated for each lesion, by placing a volume of interest around the lesion with 40% of peak activity as threshold for the automatic contouring. The patients were clinically and radiologically followed up for 21?±?11 months. Rate of progression-free survival (PFS), disease-specific survival (DSS) and incremental prognostic value of ¹⁸F-DOPA PET/CT over conventional imaging modalities were assessed by Kaplan–Meier curves and Log-Rank test. Cox regression univariate and multivariate analyses were performed for assessing predictors of prognosis.

Results

¹⁸F-DOPA PET/CT showed abnormal findings in 27 patients (45%) and resulted unremarkable in 33 (55%). PFS was significantly longer in patients with an unremarkable PET/CT scan (p?=?0.018). Similarly, an unremarkable PET/CT study was associated with a significantly longer DSS (p?=?0.04). ¹⁸F-DOPA PET/CT added prognostic value over other imaging modalities both for PFS and for DSS (p?<?0.001 and p?=?0.012, respectively). Neither semiquantitative PET parameters nor clinical or laboratory data were predictive of a worse PFS and DSS in patients with recurrent MTC.

Conclusion

¹⁸F-DOPA PET/CT scan has an important prognostic value in predicting disease progression and mortality rate.

     

Quantitative assessment of atherosclerotic plaques on <Superscript>18</Superscript>F-FDG PET/MRI: comparison with a PET/CT hybrid system

Purpose

PET with ¹⁸F-FDG has the potential to assess vascular macrophage metabolism. ¹⁸F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel ¹⁸F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of ¹⁸F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques.

Methods

The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with ¹⁸F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUV_max) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated.

Results

Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUV_max values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3?±?0.6 vs. 3.1?±?0.6; P?<?0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman’s r?=?0.67, P?<?0.01). In contrast, TBR_max values of plaque lesions were similar on PET/MRI and on PET/CT (2.2?±?0.3 vs. 2.2?±?0.3; P?=?0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman’s r?=?0.73, P?<?0.01). Considering the increasing trend in SUV_max and TBR_max values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBR_max values may also be expected with PET/MRI compared with PET/CT.

Conclusion

SUV_max and TBR_max values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUV_max and TBR_max with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI.

     

Prospective comparison of <Superscript>68</Superscript>Ga-DOTATATE and <Superscript>18</Superscript>F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases

Purpose

Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using ⁶⁸Ga-labeled somatostatin analogs (⁶⁸Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of ⁶⁸Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland.

Design

⁶⁸Ga-DOTATATE, ¹⁸F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse.

Results

The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging respectively (p?=?0.042). ⁶⁸Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than ¹⁸F-FDOPA PET/CT (26/30; p?=?0.112) and conventional imaging (24/30; p?=?0.024). ⁶⁸Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on ⁶⁸Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO).

Conclusion

⁶⁸Ga-DOTATATE PET/CT is the most sensitive tool in the detection of HNPGLs, especially SDHD-related tumors, which may be very small and fail to concentrate sufficient ¹⁸F-FDOPA. The present study further expands the use of ⁶⁸Ga-DOTATATE for all patients with HNPGLs, regardless of their genotype. ⁶⁸Ga-DOTATATE PET/CT may be inferior to ¹⁸F-FDOPA PET/CT in the detection PHEOs.

     

18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation

Purpose

Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F–fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3-octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI.

Methods

PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV_max) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard.

Results

Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85–1); specificity of 0.96 (0.82–0.99). The optimal 18F-DOPA PET SUV_max ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV_max cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93–1) for 18F-DOPA PET vs. 0.71 (0.43–0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively.

Conclusion

18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged.

     

Influence of <Superscript>18</Superscript>F-FDG PET/CT on therapy management in patients with stage III/IV malignant melanoma

Purpose

To evaluate the influence of ¹⁸F-FDG PET/CT in comparison to CT alone on treatment decisions in patients with advanced melanoma and to analyse the 5-year survival data in comparison to literature data.

Methods

Therapy management in 64 consecutive patients (primary staging n?=?52; surveillance n?=?12) with stage III/IV melanoma who underwent ¹⁸F-FDG PET/CT between 2004 and 2005 in our department was retrospectively analysed. Treatment decisions were made by two dermatooncologists for each patient twice, first based on the CT results and then based on the PET/CT results. Therapy changes based on the PET/CT results were classified as “major” (e.g. change from metastasectomy to systemic therapy) or “minor” (e.g. change from first to second line chemotherapy). The 5-year survival data of different patient cohorts were calculated.

Results

In the 52 patients in the primary staging group, the results of ¹⁸F-FDG PET/CT led to therapy change in 59 % and a major therapy change in 52 %. ¹⁸F-FDG PET/CT led to the avoidance of futile operations in 13 patients with suspicious lesions on CT that were deemed nontumorous on PET/CT. In the 12 patients in the surveillance group, the results of ¹⁸F-FDG PET/CT led to therapy change in 33 % and a major change in 17 %. The 5-year survival rates were 30 % in the entire cohort, 34 % in the primary staging group, and 17 % in the surveillance group. A significant overall survival benefit was observed in patients in whom ¹⁸F-FDG PET/CT excluded metastases or in whom metastases could be completely removed compared with patients who were not eligible for surgery (41 % vs. 10 %).

Conclusion

Primary staging of patients with stage III/IV melanoma should be performed with ¹⁸F-FDG PET/CT, leading to higher diagnostic accuracy and enabling individualized therapeutic management, especially optimal patient selection for metastasectomy. This strategy may extend long-term survival even in patients with advanced disease.

     

[<Superscript>68</Superscript>Ga]DOTATATE PET/MRI and [<Superscript>18</Superscript>F]FDG PET/CT are complementary and superior to diffusion-weighted MR imaging for radioactive-iodine-refractory differentiated thyroid cancer

Purpose

The purpose of this study was to determine whether [⁶⁸Ga]DOTATATE PET/MRI with diffusion-weighted imaging (DWI) can replace or complement [¹⁸F]FDG PET/CT in patients with radioactive-iodine (RAI)-refractory differentiated thyroid cancer (DTC).

Methods

The study population comprised 12 patients with elevated thyroglobulin and a negative RAI scan after thyroidectomy and RAI remnant ablation who underwent both [¹⁸F]FDG PET/CT and [⁶⁸Ga]DOTATATE PET/MRI within 8 weeks of each other. The presence of recurrent cancer was evaluated on a per-patient, per-organ and per-lesion basis. Histology, and prior and follow-up examinations served as the standard of reference.

Results

Recurrent or metastatic tumour was confirmed in 11 of the 12 patients. [⁶⁸Ga]DOTATATE PET(/MRI) correctly identified the tumour burden in all 11 patients, whereas in one patient local relapse was missed by [¹⁸F]FDG PET/CT. In the lesion-based analysis, overall lesion detection rates were 79/85 (93 %), 69/85 (81 %) and 27/82 (33 %) for [¹⁸F]FDG PET/CT, [⁶⁸Ga]DOTATATE PET/MRI and DWI, respectively. [¹⁸F]FDG PET(/CT) was superior to [⁶⁸Ga]DOTATATE PET(/MRI) in the overall evaluation and in the detection of pulmonary metastases. In the detection of extrapulmonary metastases, [⁶⁸Ga]DOTATATE PET(/MRI) showed a higher sensitivity than [¹⁸F]FDG PET(/CT), at the cost of lower specificity. DWI achieved only poor sensitivity and was significantly inferior to [¹⁸F]FDG PET in the lesion-based evaluation in the detection of both extrapulmonary and pulmonary metastases.

Conclusion

[¹⁸F]FDG PET/CT was more sensitive than [⁶⁸Ga]DOTATATE PET/MRI in the evaluation of RAI-refractory DTC, mostly because of its excellent ability to detect lung metastases. In the evaluation of extrapulmonary lesions, [⁶⁸Ga]DOTATATE PET(/MRI) was more sensitive and [¹⁸F]FDG PET(/CT) more specific. Furthermore, DWI did not provide additional information and cannot replace [¹⁸F]FDG PET for postoperative monitoring of patients with suspected RAI-refractory DTC.

     

Prospective evaluation of <Superscript>18</Superscript>F-FACBC PET/CT and PET/MRI versus multiparametric MRI in intermediate- to high-risk prostate cancer patients (FLUCIPRO trial)

Purpose

The purpose of this study was to evaluate ¹⁸F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa).

Methods

Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq ¹⁸F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUV_max) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans. Logan plots were used to calculate volume of distribution (V_T). The presence of PCa was estimated in 12 regions with radical prostatectomy findings as ground truth. For each imaging modality, area under the curve (AUC) for detection of PCa was determined to predict diagnostic performance. The clinical trial registration number is NCT02002455.

Results

In the visual analysis, 164/312 (53%) regions contained PCa, and 41 tumor foci were identified. PET/CT demonstrated the highest sensitivity at 87% while its specificity was low at 56%. The AUC of both PET/MRI and mpMRI significantly (p < 0.01) outperformed that of PET/CT while no differences were detected between PET/MRI and mpMRI. SUV_max and V_T of Gleason score (GS) >3 + 4 tumors were significantly (p < 0.05) higher than those for GS 3 + 3 and benign hyperplasia. A total of 442 lymph nodes were evaluable for staging, and PET/CT and PET/MRI demonstrated true-positive findings in only 1/7 patients with metastatic lymph nodes.

Conclusions

Quantitative ¹⁸F-FACBC imaging significantly correlated with GS but failed to outperform MRI in lesion detection. ¹⁸F-FACBC may assist in targeted biopsies in the setting of hybrid imaging with MRI.

     

<Superscript>18</Superscript>F-FDG PET/MRI evaluation of retroperitoneal fibrosis: a simultaneous multiparametric approach for diagnosing active disease

Purpose

The aim of this study was to evaluate integrated ¹⁸F-FDG PET/MRI as a one-stop diagnostic procedure in the assessment of (active) idiopathic retroperitoneal fibrosis (RPF)

Methods

A total of 22 examinations comprising a PET/CT scan followed by a PET/MRI scan in 17 patients (13 men, 4 women, age 58?±?11 years) with histopathologically confirmed RPF at diagnosis or during follow-up under steroid therapy were analysed in correlation with laboratory inflammation markers (ESR, CRP). The patient cohort was subdivided into two groups: 6 examinations in untreated and 16 in treated patients. Tissue formations in typically periaortic localization suggestive of RPF were visually and quantitatively evaluated. The PET analysis included the assessment of SUVmax and a qualitative score for FDG uptake in RPF tissue in relation to the uptake in the liver. MRI analysis included evaluation of the T2-weighted image signal intensity, contrast enhancement and diffusion restriction (ADC values). Mean values were compared using the Mann-Whitney U test. ADC, SUVmax and ESR values were correlated using Pearson’s correlation.

Results

MRI analysis revealed restricted diffusion in 100 % and 56 %, hyperintense T2 signal in 100 % and 31 %, and contrast enhancement in the periaortic tissue formation suggestive of RPF in 100 % and 62.5 % in the untreated and treated patients, respectively. In the qualitative and quantitative PET analysis, statistically significant differences were found for mean FDG uptake scores (2.5?±?0.8 in untreated patients and 1.1?±?0.9 in treated patients) and mean SUVmax (7.8?±?3.5 and 4.1?±?2.2, respectively). A strong correlation was found between the ADC values and SUVmax (Pearson r? ??0.65, P?=?0.0019), and between ESR and CRP values and SUVmax (both r?=?0.45, P?=?0.061).

Conclusion

Integrated ¹⁸F-FDG PET/MRI shows high diagnostic potential as a one-stop diagnostic procedure for the assessment of (active) RPF providing multiparametric supportive information.

     

Prospective comparison of <Superscript>68</Superscript>Ga-PSMA PET/CT, <Superscript>18</Superscript>F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer

Purpose

To prospectively compare diagnostic accuracies for detection of bone metastases by ⁶⁸Ga-PSMA PET/CT, ¹⁸F-NaF PET/CT and diffusion-weighted MRI (DW₆₀₀-MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR).

Methods

Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent ⁶⁸Ga-PSMA PET/CT, a ¹⁸F-NaF PET/CT and a DW₆₀₀-MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm²). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic.

Results

Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98–1.00 and 0.89–0.90 for ⁶⁸Ga-PSMA PET/CT (n?=?68 patients); 0.90, 0.90–0.98 and 0.90–0.94 for ¹⁸NaF PET/CT (n?=?67 patients); and 0.25–0.38, 0.87–0.92 and 0.59–0.62 for DW₆₀₀-MRI (n?=?60 patients). The diagnostic performance of DW₆₀₀-MRI was significantly lower than that of ⁶⁸Ga-PSMA PET/CT and ¹⁸NaF PET/CT for diagnosing bone metastases (p?<?0.01), and no significant difference in the AUC was seen between ⁶⁸Ga-PSMA PET/CT and ¹⁸NaF PET/CT (p?=?0.65).

Conclusion

⁶⁸Ga-PSMA PET/CT and ¹⁸F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW₆₀₀-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

     

Treatment response evaluation with <Superscript>18</Superscript>F-FDG PET/CT and <Superscript>18</Superscript>F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

Aim

The aim of this study was to assess the combined use of the radiotracers ¹⁸F-FDG and ¹⁸F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT).

Patients and methods

Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with ¹⁸F-FDG and ¹⁸F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD).

Results

An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, ¹⁸F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, ¹⁸F-FDG PET/CT-based treatment response revealed CR in 14 patients (¹⁸F-FDG PET/CT CR), PR in 11 patients (¹⁸F-FDG PET/CT PR) and progressive disease in four patients (¹⁸F-FDG PET/CT PD). In terms of ¹⁸F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, ¹⁸F-NaF PET/CT depicted 56 of the 129 ¹⁸F-FDG positive lesions (43 %). Follow-up ¹⁸F-NaF PET/CT showed persistence of 81.5 % of the baseline ¹⁸F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to ¹⁸F-FDG negative. Treatment response according to ¹⁸F-NaF PET/CT revealed CR in one patient (¹⁸F-NaF PET/CT CR), PR in five patients (¹⁸F-NaF PET/CT PR), SD in 12 patients (¹⁸F-NaF PET/CT SD), and PD in seven patients (¹⁸F-NaF PET/CT PD). Dynamic ¹⁸F-FDG and ¹⁸F-NaF PET/CT studies showed that SUV_average, SUV_max, as well as the kinetic parameters K₁, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p?<?0.001).

Conclusion

F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of ¹⁸F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, ¹⁸F-NaF PET/CT does not seem to add significantly to ¹⁸F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy.

     

Diagnostic value of combining <Superscript>11</Superscript>C-choline and <Superscript>18</Superscript>F-FDG PET/CT in hepatocellular carcinoma

Purpose

In this prospective study, our goal was to emphasize the diagnostic value of combining ¹¹C-choline and ¹⁸F-FDG PET/CT for hepatocellular carcinoma (HCC) in patients with chronic liver disease.

Methods

Thirty-three consecutive patients were enrolled. All patients were suspected to have HCC based on CT and/or MRI imaging. A final diagnosis was obtained by histopathological examination or by imaging alone according to American Association for the Study of Liver Disease criteria. All patients underwent PET/CT with both tracers within a median of 5 days. All lesions showing higher tracer uptake than normal liver were considered positive for HCC. We examined how tracer uptake was related to biological (serum α-fetoprotein levels) and pathological (differentiation status, peritumoral capsule and vascular invasion) prognostic markers of HCC, as well as clinical observations at 6 months (recurrence and death).

Results

Twenty-eight HCC, four cholangiocarcinomas and one adenoma were diagnosed. In the HCC patients, the sensitivity of ¹¹C-choline, ¹⁸F-FDG and combined ¹¹C-choline and ¹⁸F-FDG PET/CT for the detection of HCC was 75 %, 36 % and 93 %, respectively. Serum α-fetoprotein levels >200 ng/ml were more frequent among patients with ¹⁸F-FDG-positive lesions than those with ¹⁸F-FDG-negative lesions (p?<?0.05). Early recurrence (n=2) or early death (n=5) occurred more frequently in patients with ¹⁸F-FDG-positive lesions than in those with ¹⁸F-FDG-negative lesions (p?<?0.05).

Conclusion

The combined use of ¹¹C-choline and ¹⁸F-FDG PET/CT detected HCC with high sensitivity. This approach appears to be of potential prognostic value and may facilitate the selection of patients for surgical resection or liver transplantation.

     

<Superscript>18</Superscript>F-FDG and <Superscript>18</Superscript>F-FLT PET/CT imaging in the characterization of mediastinal lymph nodes

Purpose

There is currently no single modality for accurate characterization of enlarged mediastinal lymph nodes into benign or malignant. Recently ¹⁸F-fluorothymidine (FLT) has been used as a proliferation marker. In this prospective study, we examined the role of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) and ¹⁸F-FLT PET/CT in categorizing mediastinal lymph nodes as benign or malignant.

Materials and methods

A total of 70 consecutive patients with mediastinal lymphadenopathy detected on computed tomography (CT) or chest radiograph underwent whole body ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT (within 1 week of each other). Lymph nodal tracer uptake was determined by calculation of standardized uptake value (SUV) with both the tracers. Results of PET/CT were compared with histopathology of the lymph nodes.

Results

Histopathology results showed thirty-seven patients with sarcoidosis, seven patients with tuberculosis, nine patients with non-small cell lung cancer, five patients with Hodgkin’s lymphoma and twelve patients with non-Hodgkin’s lymphoma. The mean FDG SUV_max of sarcoidosis, tuberculosis, Hodgkin’s and non-Hodgkin’s lymphoma was 12.7, 13.4, 8.2, and 8.8, respectively, and the mean FLT SUV_max was 6.0, 5.4, 4.4, and 3.8, respectively. It was not possible to characterize mediastinal lymphadenopathy as benign or malignant solely based on FDG SUV_max values (p > 0.05) or FLT SUV_max values (p > 0.05). There was no significant difference in FDG uptake (p > 0.9) or FLT uptake (p > 0.9) between sarcoidosis and tuberculosis. In lung cancer patients, the FDG SUV_max and FLT SUV_max of those lymph nodes with tumor infiltration on biopsy was 6.7 and 3.9, respectively, and those without nodal infiltration was 6.4 and 3.7, respectively, and both the tracers were not able to characterize the nodal status as malignant or benign (p > 0.05).

Conclusion

Though ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT reflect different aspects of biology, i.e., proliferation and metabolism, respectively, neither tracer could provide satisfactory categorization of benign and malignant lymph nodes. The results of this study clearly suggest that differentiation of mediastinal nodes into benign and malignant solely based on SUV_max values cannot be relied upon, especially in settings where tuberculosis and sarcoidosis are common.

     

Quantitative <Superscript>18</Superscript>F-DOPA PET/CT in pheochromocytoma: the relationship between tumor secretion and its biochemical phenotype

Introduction

¹⁸F-FDOPA illustrates the properties of uptake and storage of catecholamines in pheochromocytomas (PHEOs). Until now, the relationship between ¹⁸F-FDOPA quantitative parameters and a PHEO secretory profile has not been specifically evaluated.

Materials and methods

Fifty-six patients (56% females, median age: 47.5 yrs) with non-metastatic PHEO, evaluated by ¹⁸F-FDOPA PET/CT, were included in this retrospective study. Forty-five patients had negative genetic testing (80.4%); five patients (8.9%) had RET, two patients (3.6%) had SDHB, two had SDHD (3.6%), one patient (1.8%) had NF1, and one patient had a VHL (1.8%) mutation. Correlation between ¹⁸F-FDOPA metabolic parameters (tumor SUVmax, tumor SUVmean, tumor SUVmax/liver SUVmax, MTV 42%, total lesion uptake), urinary metanephrines (MNs), and plasma chromogranin A (CgA) were evaluated.

Results

All patients had positive ¹⁸F-FDOPA PET/CT. On univariate analysis, there was a strong correlation between all metabolic parameters and urinary MNs and plasma chromogranin A (CgA). The highest correlations were observed between total lesion (TL) uptake and the value of urinary MNs regardless of their nature (p = 8.10^?15 and r = 0.80) and between MTV 42% and plasma CgA levels (p = 2.10^?9, r = 0.74). On multivariate analysis, the correlation of uptake parameters and CgA levels did not persist further due to the relation of CgA and tumor diameter. A correlation between TL uptake and the normetanephrine/metanephrine ratio (NMN/MN) was also found, a finding that was in accordance with in vitro studies, which were found to have a higher catecholamine content in epinephrine producing PHEOs.

Conclusion

This retrospective study shows a correlation between ¹⁸F-FDOPA uptake, especially using TL uptake, urinary MNs, and a PHEO biochemical phenotype. This illustrates that beyond its localization value, ¹⁸F-FDOPA PET further enables PHEO characterization at a specific metabolic level.

     

Diagnostic Value of <Superscript>18</Superscript>F-FDG PET/CT and MRI in the Preoperative Evaluation of Uterine Carcinosarcoma

Purpose

This study aimed to compare the diagnostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and magnetic resonance imaging (MRI) in the preoperative evaluation of uterine carcinosarcoma.

Methods

Fifty-four women with pathologically confirmed uterine carcinosarcoma who underwent preoperative FDG PET/CT and MRI from June 2006 to November 2016 were included. Pathologic findings from primary tumor lesions, para-aortic and pelvic lymph node (LN) areas, and peritoneal seeding lesions were compared with the FDG PET/CT and MRI findings. The maximum standardized uptake value (SUVmax) of the primary tumor and LN was obtained. The tumor-to-liver ratio (TLR) was calculated by dividing the SUVmax of the primary tumor or LN by the mean SUV of the liver.

Results

For detecting primary tumor lesions (n?=?54), the sensitivity and accuracy of FDG PET/CT (53/54) and MRI (53/54) were 98.2%. The sensitivity, specificity, and accuracy of FDG PET/CT versus MRI were as follows: 63.2% (12/19) versus 26.3% (5/19), 100% (35/35) versus 100% (35/35), and 87.0% versus 74.0%, respectively, for pelvic LN areas (p?=?0.016); 85.7% (12/14) versus 42.9% (6/14), 90% (36/40) versus 97.5% (39/40), and 88.9% versus 83.3%, respectively, for para-aortic LN areas (p?=?0.004); and 59.4% (19/32) versus 50% (16/32), 100% (22/22) versus 100% (22/22), and 75.9% versus 70.4%, respectively, for peritoneal seeding lesions (p?=?0.250). For distant metastasis, the sensitivity, specificity, and accuracy of FDG PET/CT were 100 (8/8), 97.8 (45/46), and 98.2%, respectively.

Conclusions

FDG PET/CT showed superior diagnostic accuracy compared to MRI in detecting pelvic and para-aortic LN metastasis in patients with uterine carcinosarcoma. Moreover, FDG PET/CT facilitated the identification of distant metastasis.

     

Usefulness of MRI-assisted metabolic volumetric parameters provided by simultaneous <Superscript>18</Superscript>F-fluorocholine PET/MRI for primary prostate cancer characterization

Purpose

The aim of this study was to determine the usefulness of MRI-assisted positron emission tomography (PET) parameters provided by simultaneous ¹⁸F-fluorocholine (FCH) PET/MRI for characterization of primary prostate cancer.

Methods

Thirty patients with localized prostate cancer (mean age 69.4?±?6.7 years) confirmed by biopsy were prospectively enrolled for simultaneous PET/MRI imaging. The patients underwent ¹⁸F-FCH PET/MRI 1 week before undergoing total prostatectomy. Multiple parameters of diffusion-weighted MRI [minimum and mean apparent diffusion coefficient (ADC_min and ADC_mean)], metabolic PET [maximum and mean standardized uptake value (SUV_max and SUV_mean)], and metabolic volumetric PET [metabolic tumor volume (MTV) and uptake volume product (UVP)] were compared with laboratory, pathologic, and immunohistochemical (IHC) features of the prostate cancer specimen. PET parameters were divided into two categories as follows: volume of interest (VOI) of prostate by SUV cutoff 2.5 (SUV_max, SUV_mean, MTV_SUV, and UVP_SUV) and MRI-assisted VOI of prostate cancer (SUV_maxMRI, SUV_meanMRI, MTV_MRI, and UVP_MRI).

Results

The rates of prostate cancer-positive cases identified by MRI alone, ¹⁸F-FCH PET alone, and ¹⁸F-FCH PET/MRI were 83.3, 80.0, and 93.3 %, respectively. Among the multiple PET/MRI parameters, MTV_MRI showed fair correlation with serum prostate-specific antigen (PSA; r?=?0.442, p?=?0.014) and highest correlation with tumor volume (r?=?0.953, p?<?0.001). UVP_MRI showed highest correlation with serum PSA (r?=?0.531, p?=?0.003), good correlation with tumor volume (r?=?0.908, p?<?0.001), and it was significantly associated with Gleason score (p?=?0.041). High MTV_MRI and UVP_MRI values were significant for perineural invasion, lymphatic invasion, extracapsular extension, seminal vesicle invasion, and positive B-cell lymphoma 2 (Bcl-2) expression (all p?<?0.05).

Conclusion

Simultaneous ¹⁸F-FCH PET/MRI demonstrated a better diagnostic value for localized prostate cancer detection than each individual modality. MRI-assisted metabolic volumetric PET parameters (MTV_MRI and UVP_MRI) provided more accurate characterization of prostate cancer than conventional PET and MRI parameters.

     

<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.

     

Role of <Superscript>18</Superscript>F-FDG PET/CT in patients affected by Langerhans cell histiocytosis

Purpose

Langerhans cell histiocytosis (LCH) is a rare hematological disorder for which the utility of¹⁸F-FDG PET/CT is unclear. Our aim was to explore the metabolic features of LCH and the possible role of¹⁸F-FDG PET/CT in LCH evaluation.

Materials and methods

We found 17 patients with histologically proven LCH who underwent 17¹⁸F-FDG PET/CT scans for staging and 42 scans for restaging/follow-up purposes. PET/CT results were compared with those obtained from other conventional imaging modalities (bone scintigraphy, plain radiogram, computed tomography, magnetic resonance).

Results

¹⁸F-FDG PET/CT was positive in 15/17 patients, and it detected 36/37 lesions; all bone and extraskeletal lesions, except for a cecal lesion, were¹⁸F-FDG-avid. Only 1/4 of the patients with lung LCH had hypermetabolic lesions. The average SUV_max of the FDG-avid lesions was 7.3 ± 6.7, the average lesion-to-liver SUV_max ratio was 3.4 ± 2.5, and the average lesion-to-blood pool SUV_max ratio was 4 ± 3.2. In comparison to other imaging methods,¹⁸F-FDG PET/CT detected additional lesions or was able to evaluate treatment response earlier in 33/74 cases; it was confirmatory in 38/74 and detected fewer lesions in 3/74 (all three with lung LCH).

Conclusions

¹⁸F-FDG PET/CT seems to be useful for evaluating LCH when compared to conventional imaging, except in pulmonary cases. It can be used both for staging and restaging purposes.