Role of 18F-FDG PET/CT in the prediction of gastric cancer recurrence after curative surgical resection

Purpose

The study evaluated the role of preoperative ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in the prediction of recurrent gastric cancer after curative surgical resection.

Methods

A total of 271 patients with gastric cancer who underwent ¹⁸F-FDG PET/CT and subsequent curative surgical resection were enrolled. All patients underwent follow-up for cancer recurrence with a mean duration of 24?±?12?months. ¹⁸F-FDG PET/CT images were visually assessed and, in patients with positive ¹⁸F-FDG cancer uptake, the maximum standardized uptake value (SUV_max) of cancer lesions was measured. ¹⁸F-FDG PET/CT findings were tested as prognostic factors for cancer recurrence and compared with conventional prognostic factors. Furthermore, ¹⁸F-FDG PET/CT findings were assessed as prognostic factors according to histopathological subtypes.

Results

Of 271 patients, 47 (17?%) had a recurrent event. Positive ¹⁸F-FDG cancer uptake was shown in 149 patients (55?%). Tumour size, depth of invasion, presence of lymph node metastasis, positive ¹⁸F-FDG uptake and SUV_max were significantly associated with tumour recurrence in univariate analysis, while only depth of invasion, positive ¹⁸F-FDG uptake and SUV_max had significance in multivariate analysis. The 24-month recurrence-free survival rate was significantly higher in patients with negative ¹⁸F-FDG uptake (95?%) than in those with positive ¹⁸F-FDG uptake (74?%; p?18F-FDG uptake was a significant prognostic factor in patients with tubular adenocarcinoma (p?=?0.003) or poorly differentiated adenocarcinoma (p?=?0.0001). However, only marginal significance was shown in patients with signet-ring cell carcinoma and mucinous carcinoma (p?=?0.05).

Conclusion

¹⁸F-FDG uptake of gastric cancer is an independent and significant prognostic factor for tumour recurrence. ¹⁸F-FDG PET/CT could provide effective information on the prognosis after surgical resection of gastric cancer, especially in tubular adenocarcinoma and poorly differentiated adenocarcinoma.     

Factors affecting intrapatient liver and mediastinal blood pool 18F-FDG standardized uptake value changes during ABVD chemotherapy in Hodgkin’s lymphoma

Purpose

The aim of our study was to assess the intrapatient variability of 2-deoxy-2-(¹⁸F)-fluoro-D-glucose (¹⁸F-FDG) uptake in the liver and in the mediastinum among patients with Hodgkin’s lymphoma (HL) treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy (CHT).

Methods

The study included 68 patients (30 men, 38 women; mean age 32?±?11 years) with biopsy-proven HL. According to Ann Arbor criteria, 6 were stage I, 34 were stage II, 12 were stage 3 and 16 were stage 4. All of them underwent a baseline (PET0) and an interim (PET2) ¹⁸F-FDG whole-body positron emission tomography (PET)/CT. All patients were treated after PET0 with two ABVD cycles for 2 months that ended 15?±?5 days prior to the PET2 examination. All patients were further evaluated 15?±?6 days after four additional ABVD cycles (PET6). None of the patients presented a serum glucose level higher than 107 mg/dl. The mean and maximum standardized uptake values (SUV) of the liver and mediastinum were calculated using the same standard protocol for PET0, PET2 and PET6, respectively. Data were examined by means of the Wilcoxon matched pairs test and linear regression analysis.

Results

The main results of our study were an increased liver SUV_mean in PET2 (1.76?±?0.35) as compared with that of PET0 (1.57?±?0.31; p?<?0.0001) and PET6 (1.69?±?0.28; p?=?0.0407). The same results were obtained when considering liver SUV_max in PET2 (3.13?±?0.67) as compared with that of PET0 (2.82?±?0.64; p?<?0.0001) and PET6 (2.96?±?0.52; p?=?0.0105). No significant differences were obtained when comparing mediastinum SUV_mean and SUV_max in PET0, PET2 and PET6 (p?>?0.05). Another finding is a relationship in PET0 between liver SUV_mean and SUV_max with the stage, which was lower in those patients with advanced disease (r ²?=?0.1456 and p?=?0.0013 for SUV_mean and r ²?=?0.1277 and p?=?0.0028 for SUV_max).

Conclusion

The results of our study suggest that liver ¹⁸F-FDG uptake is variable in patients with HL during the CHT treatment and the disease course and should be considered carefully when used to define the response to therapy in the interim PET in HL.     

PET/CT studies of multiple myeloma using 18 F-FDG and 18 F-NaF: comparison of distribution patterns and tracers’ pharmacokinetics

Objective

The aim of this prospective study is to evaluate the combined use of fluorine-18 fluorodeoxyglucose (¹⁸?F-FDG) and fluorine-18 sodium fluoride (¹⁸?F-NaF) PET/CT in the skeletal assessment of patients with multiple myeloma (MM) and to compare the efficacy of these two PET tracers regarding detection of myeloma-indicative osseous lesions.

Patients and methods

The study includes 60 patients with multiple myeloma (MM) diagnosed according to standard criteria. All patients underwent dynamic (dPET/CT) scanning of the pelvis as well as whole body PET/CT studies with both tracers. The interval between the two exams was one day. Sites of focal increased ¹⁸?F-FDG uptake were considered as highly suspicious of myelomatous involvement. The lesions detected on the ¹⁸?F-NaF PET/CT scans were then correlated with those detected on ¹⁸?F-FDG PET/CT, which served as a reference. Moreover, the ¹⁸?F-FDG PET/CT results were also correlated with the low-dose CT findings. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a 2-tissue compartment model and a non-compartmental approach.

Results

Whole body ¹⁸?F-FDG PET/CT revealed approximately 343 focal lesions while ¹⁸?F-NaF PET/CT revealed 135 MM-indicative lesions (39 % correlation). CT demonstrated 150 lesions that correlated with those in ¹⁸?F-FDG PET/CT (44 % correlation). Six patients demonstrated a diffuse pattern of disease with ¹⁸?F-FDG, while 15 of them had a mixed (diffuse and focal) pattern of skeletal ¹⁸?F-FDG uptake. A high number of degenerative, traumatic and arthritic disease lesions were detected with ¹⁸?F-NaF PET/CT. In three patients with multiple focal ¹⁸?F-FDG-uptake, ¹⁸?F-NaF PET/CT failed to demonstrate any bone lesion. The dPET/CT scanning of the pelvic area with ¹⁸?F-FDG and ¹⁸?F-NaF revealed 77 and 24 MM-indicative lesions, respectively. Kinetic analysis of ¹⁸?F-FDG revealed the following mean values: SUV_aver?=?5.1, k₁?=?0.37 (1/min), k₃?=?0.10 (1/min), V_B?=?0.06, influx?=?0.04 (1/min), FD?=?1.28; the respective values for ¹⁸?F-NaF were SUV_average?=?10.7, k₁?=?0.25 (1/min), k₃?=?0.34 (1/min), V_B?=?0.02, influx?=?0.10 (1/min), FD?=?1.37. Apart from the correlation between V_B of ¹⁸?F-FDG and k₁ of ¹⁸?F-NaF (r?=?0.54), no other significant correlation was observed between the two tracers’ kinetic parameters. We found a significant correlation between FD and SUV_average (r?=?0.93), FD and SUV_max (r?=?0.80), FD and influx ( r?=?0.85), as well as between influx and SUV_average (r?=?0.74) for ¹⁸?F-FDG. In ¹⁸?F-NaF we observed the most significant correlations between FD and SUV_average (r?=?0.97), FD and SUV_max (r?=?0.87), and between influx and k₁ (r?=?0.72).

Conclusion

The combined use of ¹⁸?F-FDG PET/CT and ¹⁸?F-NaF PET/CT provides different molecular information regarding the biological processes that take place in a MM osseous lesion. ¹⁸?F-FDG PET/CT proved to be a more specific biomarker than ¹⁸?F-NaF PET/CT in multiple myeloma skeletal assessment.     

Preoperative PET/CT standardized FDG uptake values of pelvic lymph nodes as a significant prognostic factor in patients with endometrial cancer

Purpose

Using integrated PET/CT, we evaluated the prognostic relevance of preoperative pelvic lymph node (LN) ¹⁸F-FDG uptake in endometrioid endometrial cancer.

Methods

We retrospectively reviewed patients with pathologically proven endometrial cancer who underwent preoperative ¹⁸F-FDG PET/CT scans to evaluate the prognostic significance of PET/CT parameters and other clinicopathological variables. We used Cox proportional hazards regression to examine the relationship between recurrence and the maximum standardized uptake value (SUV_max) in pelvic LNs (SUV_LN) on FDG PET/CT.

Results

Clinical data, treatment modalities and results were reviewed in 70 eligible patients. The median postsurgical follow-up was 29 months (range 6 to 95 months). Receiver-operating characteristic analysis identified the significant SUV_LN cut-off value as 15. The SUV_LN correlated with FIGO stage (P?<?0.001), LN metastasis (P?<?0.001), lymphovascular space invasion (P?<?0.001), SUV_tumour (P?=?0.001), metastatic LN size (P?=?0.004), primary tumour size (P?=?0.012), tumour grade (P?=?0.015) and depth of tumour invasion (P?=?0.035). Regression analysis showed a statistically significant association between recurrence and SUV_LN (P?=?0.002). Recurrence differed significantly (P?<?0.001) between patients with SUV_LN >15 and those with SUV_LN ≤15.

Conclusion

Preoperative pelvic LN FDG uptake exhibited a strong significant association with recurrence of endometrioid endometrial cancer.     

Anatomical and functional volume concordance between FDG PET,and T2 and diffusion-weighted MRI for cervical cancer: a hybrid PET/MR study

Purpose

To evaluate the concordance among ¹⁸F-FDG PET imaging, MR T2-weighted (T2-W) imaging and apparent diffusion coefficient (ADC) maps with diffusion-weighted (DW) imaging in cervical cancer using hybrid whole-body PET/MR.

Methods

This study prospectively included 35 patients with cervical cancer who underwent pretreatment ¹⁸F-FDG PET/MR imaging. ¹⁸F-FDG PET and MR images were fused using standard software. The percent of the maximum standardized uptake values (SUV_max) was used to contour tumours on PET images, and volumes were calculated automatically. Tumour volumes measured on T2-W and DW images were calculated with standard techniques of tumour area multiplied by the slice profile. Parametric statistics were used for data analysis.

Results

FDG PET tumour volumes calculated using SUV_max (14.30?±?4.70) and T2-W imaging volume (33.81?±?27.32 cm³) were similar (P?>?0.05) at 35 % and 40 % of SUV_max (32.91?±?18.90 cm³ and 27.56?±?17.19 cm³ respectively) and significantly correlated (P?<?0.001; r?=?0.735 and 0.766). The mean DW volume was 30.48?±?22.41 cm³. DW volumes were not significantly different from FDG PET volumes at either 35 % SUV_max or 40 % SUV_max or from T2-W imaging volumes (P?>?0.05). PET subvolumes with increasing SUV_max cut-off percentage showed an inverse change in mean ADC values on DW imaging (P?<?0.001, ANOVA).

Conclusion

Hybrid PET/MR showed strong volume concordance between FDG PET, and T2-W and DW imaging in cervical cancer. Cut-off at 35 % or 40 % of SUV_max is recommended for ¹⁸F-FDG PET/MR SUV-based tumour volume estimation. The linear tumour subvolume concordance between FDG PET and DW imaging demonstrates individual regional concordance of metabolic activity and cell density.     

Evaluation of intratumoural heterogeneity on 18F-FDG PET/CT for characterization of peripheral nerve sheath tumours in neurofibromatosis type 1

Purpose

The aim of the study was to evaluate the potential usefulness of intratumoural tracer uptake heterogeneity on ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT as compared to a cut-off maximum standardized uptake value (SUV_max) for characterization of peripheral nerve sheath tumours (PNSTs) in neurofibromatosis type 1 (NF1).

Methods

Fifty patients suffering from NF1 were examined by ¹⁸F-FDG PET/CT. Intralesional tracer uptake was analysed qualitatively and semi-quantitatively by measuring the mean and maximum SUV. Uptake heterogeneity was graded qualitatively using a three-point scale and semi-quantitatively by calculating an SUV-based heterogeneity index (HI_SUV). Cohen’s κ was used to determine inter- and intra-rater agreement. Histopathological evaluation and clinical as well as radiological follow-up examinations served as the reference standards.

Results

A highly significant correlation between the degree of intratumoural uptake heterogeneity on ¹⁸F-FDG PET and malignant transformation of PNSTs was observed (p?<?0.0001). Semi-quantitative HI_SUV was significantly higher in malignant PNSTs (MPNSTs) than in benign tumours (p?=?0.0002). Both intralesional heterogeneity and SUV_max could be used to identify malignant tumours with a sensitivity of 100 %. Cohen’s κ was 0.86 for inter-rater agreement and 0.88 for intra-rater agreement on heterogeneity.

Conclusion

MPNSTs in patients with NF1 demonstrate considerable intratumoural uptake heterogeneity on ¹⁸F-FDG PET/CT. Assessment of tumour heterogeneity is highly reproducible. Both tumour heterogeneity and a cut-off SUV_max may be used to sensitively identify malignant PNSTs, but the specificity is higher for the latter. A combination of both methods leads to a non-significant improvement in diagnostic performance.     

18F-FDG uptake in breast cancer correlates with immunohistochemically defined subtypes

Objectives

To determine whether a correlation exists between maximum standardized uptake value (SUV_max) on ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) and the subtypes of breast cancer.

Methods

This retrospective study involved 548 patients (mean age 51.6 years, range 21–81 years) with 552 index breast cancers (mean size 2.57 cm, range 1.0–14.5 cm). The correlation between ¹⁸F-FDG uptake in PET/CT, expressed as SUV_max, and immunohistochemically defined subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative) was analyzed.

Results

The mean SUV_max value of the 552 tumours was 6.07?±?4.63 (range 0.9–32.8). The subtypes of the 552 tumours were 334 (60 %) luminal A, 66 (12 %) luminal B, 60 (11 %) HER2 positive and 92 (17 %) triple negative, for which the mean SUV_max values were 4.69?±?3.45, 6.51?±?4.18, 7.44?±?4.73 and 9.83?±?6.03, respectively. In a multivariate regression analysis, triple-negative and HER2-positive tumours had 1.67-fold (P?<?0.001) and 1.27-fold (P?=?0.009) higher SUV_max values, respectively, than luminal A tumours after adjustment for invasive tumour size, lymph node involvement status and histologic grade.

Conclusion

FDG uptake was independently associated with subtypes of invasive breast cancer. Triple-negative and HER2-positive breast cancers showed higher SUV_max values than luminal A tumours.

Key Points

? ¹⁸ F-FDG PET demonstrates increased tissue glucose metabolism, a hallmark of cancers. ? Immunohistochemically defined subtypes appear significantly associated with FDG uptake (expressed as SUV _max ). ? Triple-negative tumours had 1.67-fold higher SUV _max values than luminal A tumours. ? HER2-positive tumours had 1.27-fold higher SUV _max values than luminal A tumours.     

18F-FDG PET/CT is a valuable tool for relapsing polychondritis diagnose and therapeutic response monitoring

Objectives

To retrospectively investigate the role of ¹⁸ F–fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) for the diagnosis and therapeutic response in relapsing polychondritis (RP) patients.

Methods

¹⁸F-FDG PET/CT findings were reviewed in six RP patients. The initial scans were performed for all patients, follow-up scans were performed during steroid therapy for five patients. Changes in the abnormal lesions and the maximal standard uptake value (SUV_max) were analyzed.

Results

The initial PET/CT scans revealed intense FDG uptake in the cartilages for all six patients. The lesions of abnormal FDG uptake were tracheal/bronchial cartilage (n = 4), costicartilage (n = 4), nasal cartilage (n = 3), cricoid cartilage (n = 3), auricular cartilage (n = 3), arytenoid cartilage (n = 3), thyroid cartilage (n = 2), hyoid cartilage (n = 1) and mediastinum lymph node (n = 1). The mean visual score and the mean SUV_max were 2.96 ± 0.20 and 4.10 ± 0.6. The intense uptake reduced or disappeared during steroid therapy for five patients, the mean visual score and the mean SUV_max were 1.58 ± 1.4 and 1.51 ± 1.4.

Conclusions

¹⁸F-FDG PET/CT enables the acquisition of both morphologic and glucose metabolic of the related cartilage structures. It plays a valuable role in assessing almost all cartilage and detecting RP, which is a better selection of a biopsy site as well as therapeutic response monitoring.     

Prognostic value of 18F-FDG PET/CT in patients with soft tissue sarcoma: comparisons between metabolic parameters

Objectives

To investigate the relationship between volume-based PET parameters and prognosis in patients with soft tissue sarcoma (STS).

Methods

We retrospectively reviewed 55 patients with pathologically proven STS who underwent pretreatment with ¹⁸?F-Fluorodeoxyglucose (¹⁸F-FDG) PET/CT. The maximum standardized uptake value (SUV_max), average SUV (SUV_avg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary tumors were measured using a threshold SUV as liver activity for determining the boundary of tumors. Univariate and multivariate survival analyses for overall survival were performed according to the metabolic parameters and other clinical variables.

Results

Cancer-related death occurred in 19 of 55 patients (35 %) during the follow-up period (29?±?23 months). On univariate analysis, AJCC stage (stage IV vs. I-III, hazard ratio (HR)?=?2.837, p?=?0.028), necrosis (G2 vs. G0-G1, HR?=?3.890, p?=?0.004), SUV_max (1 unit - increase, HR?=?1.146, p?=?0.008), SUV_avg (1 unit - increase, HR?=?1.469, p?=?0.032) and treatment modality (non-surgical therapy vs. surgery, HR?=?4.467, p?=?0.002) were significant predictors for overall survival. On multivariate analyses, SUV_max (HR?=?1.274, p?=?0.015), treatment modality (HR?=?3.353, p?=?0.019) and necrosis (HR?=?5.985, p?=?0.006) were identified as significant independent prognostic factors associated with decreased overall survival.

Conclusions

The SUV_max of the primary tumor is a significant independent metabolic prognostic factor for overall survival in patients with STS. Volume-based PET parameters may not add prognostic information outside of the SUV_max.     

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.

     

Standardized added metabolic activity (SAM) IN 18F-FDG PET assessment of treatment response in colorectal liver metastases

Purpose

Standardized added metabolic activity (SAM) is a PET parameter for assessing the total metabolic load of malignant processes, avoiding partial volume effects and lesion segmentation. The potential role of this parameter in the assessment of response to chemotherapy and bevacizumab was tested in patients with metastatic colorectal cancer with potentially resectable liver metastases (mCRC).

Methods

¹⁸F-FDG PET/CT was performed in 18 mCRC patients with liver metastases before treatment and after five cycles of FOLFOX/FOLFIRI and bevacizumab. Of the 18 patients, 16 subsequently underwent resection of liver metastases. Baseline and follow-up SUV_max, and SAM as well as reduction in SUV_max (?SUV_max) and SAM (?SAM) of all liver metastases were correlated with morphological response, and progression-free and overall survival (PFS and OS).

Results

A significant reduction in metabolic activity of the liver metastases was seen after chemotherapy with a median ?SUV_max of 25.3 % and ?SAM of 94.5 % (p?=?0.033 and 0.003). Median baseline SUV_max and SAM values were significantly different between morphological responders and nonresponders (3.8 vs. 7.2, p?=?0.021; and 34 vs. 211, p?=?0.002, respectively), but neither baseline PET parameters nor morphological response was correlated with PFS or OS. Follow-up SUV_max and SAM as well as ?SAM were found to be prognostic factors. The median PFS and OS in the patient group with a high follow-up SUV_max were 10.4 months and 32 months, compared to a median PFS of 14.7 months and a median OS which had not been reached in the group with a low follow-up SUV_max (p?=?0.01 and 0.003, respectively). The patient group with a high follow-up SAM and a low ?SAM had a median PFS and OS of 9.4 months and 32 months, whereas the other group had a median PFS of 14.7 months and a median OS which had not been reached (p?=?0.002 for both PFS and OS).

Conclusion

¹⁸F-FDG PET imaging is a useful tool to assess treatment response and predict clinical outcome in patients with mCRC who undergo chemotherapy before liver metastasectomy. Follow-up SUV_max, follow-up SAM and ?SAM were found to be significant prognostic factors for PFS and OS.     

Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by 18F-FDG PET/CT in squamous cell carcinoma of the oral cavity

Purpose

Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from ¹⁸F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by ¹⁸F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC.

Methods

Of 162 patients with OSCC evaluated preoperatively by ¹⁸F-FDG PET/CT, 105 who underwent definitive surgery with or without adjuvant therapy were eligible. Maximum standardized uptake value (SUV_max), MTV and TLG were measured. For calculation of MTV, 3-D regions of interest were drawn and a SUV threshold of 2.5 was used for defining regions. Univariate and multivariate analyses identified clinicopathological and imaging variables associated with OM, disease-free survival (DFS) and overall survival (OS).

Results

The median (range) SUV_max, MTV and TLG were 7.3 (0.7–41.9), 4.5 ml (0.7–115.1 ml) and 18.3 g (2.4–224.1 g), respectively. Of 53 patients with clinically negative lymph nodes, OM was detected in 19 (36 %). By univariate and multivariate analyses, MTV (P?=?0.018) and TLG (P?=?0.011) were both independent predictive factors for OM, although they were not independent of each other. The 4-year DFS and OS rates were 53.0 % and 62.0 %, respectively. Univariate and multivariate analyses revealed that MTV (P?=?0.001) and TLG (P?=?0.006), with different cut-off levels, were both independent predictive factors for DFS, although they were not independent of each other, and MTV (P?=?0.001), TLG (P?=?0.002) and the involved resection margin (P?=?0.007) were independent predictive factors for OS.

Conclusion

Pretreatment MTV and TLG may be useful in stratifying the likelihood of survival and predicting OM in OSCC.     

18F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

Purpose

PET is a powerful tool for assessing targeted therapy. Since ¹⁸F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated ¹⁸F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial.

Methods

Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUV_max, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods.

Results

Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P?=?0.011) and SUV_max (P?=?0.038) calculated before pRAIT and impact on DT (P?=?0.034), RECIST (P?=?0.009), PET (P?=?0.009), and combined response (P?=?0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC diagnosis.

Conclusion

¹⁸F-FDG PET appeared as the most potent and simplest prognostic method to predict survival in patients with progressive MTC treated with pRAIT. Biomarker DT before pRAIT also appeared as an independent prognostic factor, but no benefit was found by adding morphological and biomarker evaluation to PET assessment.     

Diagnostic accuracy of 68Ga-DOTANOC PET/CT imaging in pheochromocytoma

Purpose

The purpose of the present study was to evaluate the diagnostic accuracy of ⁶⁸Ga-DOTANOC positron emission tomography (PET)/CT in patients with suspicion of pheochromocytoma.

Methods

Data of 62 patients [age 34.3?±?16.1 years, 14 with multiple endocrine neoplasia type 2 (MEN2)] with clinical/biochemical suspicion of pheochromocytoma and suspicious adrenal lesion on contrast CT (n?=?70), who had undergone ⁶⁸Ga-DOTANOC PET/CT, were retrospectively analyzed. PET/CT images were analyzed visually as well as semiquantitatively, with measurement of maximum standardized uptake value (SUV_max), SUV_mean, SUV_max/SUV_liver, and SUV_mean/SUV_liver. Results of PET/CT were compared with ¹³¹I-metaiodobenzylguanidine (MIBG) imaging, which was available in 40 patients (45 lesions). Histopathology and/or imaging/clinical/biochemical follow-up (minimum 6 months) was used as reference standard.

Results

The sensitivity, specificity, and accuracy of ⁶⁸Ga-DOTANOC PET/CT was 90.4, 85, and 88.7 %, respectively, on patient-based analysis and 92, 85, and 90 %, respectively, on lesion-based analysis. ⁶⁸Ga-DOTANOC PET/CT showed 100 % accuracy in patients with MEN2 syndrome and malignant pheochromocytoma. On direct comparison, lesion-based accuracy of ⁶⁸Ga-DOTANOC PET/CT for pheochromocytoma was significantly higher than ¹³¹I-MIBG imaging (91.1 vs 66.6 %, p?=?0.035). SUV_max was higher for pheochromocytomas than other adrenal lesions (p?=?0.005), MEN2-associated vs sporadic pheochromocytoma (p?=?0.012), but no difference was seen between benign vs malignant pheochromocytoma (p?=?0.269).

Conclusion

⁶⁸Ga-DOTANOC PET/CT shows high diagnostic accuracy in patients with suspicion of pheochromocytoma and is superior to ¹³¹I-MIBG imaging for this purpose. Best results of ⁶⁸Ga-DOTANOC PET/CT are seen in patients with MEN2-associated and malignant pheochromocytoma.     

Correlation of breast cancer subtypes,based on estrogen receptor,progesterone receptor,and HER2, with functional imaging parameters from 68Ga-RGD PET/CT and 18F-FDG PET/CT

Purpose

Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes.

Methods

In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6?±?7.5 years old). ⁶⁸Ga-Labeled arginine-glycine-aspartic acid (RGD) and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUV_max and SUV_avg) from RGD PET/CT and SUV_max and SUV_avg from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2?, ER/PR+,Her2+, ER/PR?,Her2+, and ER/PR?,Her2?), were considered.

Results

Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88?±?8.73 vs 10.48?±?6.01, p?=?0.02 for SUV_max; 9.40?±?5.19 vs 5.92?±?4.09, p?=?0.02 for SUV_avg) and the PR-negative group (8.37?±?4.94 vs 4.79?±?3.93, p?=?0.03 for SUV_avg). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42?±?0.59 vs 2.90?±?0.75, p?=?0.04 for SUV_max; 1.60?±?0.38 vs 1.95?±?0.53, p?=?0.04 for SUV_avg) and showed a significant positive correlation with the HER2/CEP17 ratio (r?=?0.38, p?=?0.03 for SUV_max and r?=?0.46, p?<?0.01 for SUV_avg). FDG PET parameters showed significantly higher values in the ER/PR?,Her2? subgroup versus the ER/PR+,Her2? or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER/PR?,Her2? subgroup versus the other subgroups. There was no correlation between FDG and RGD PET parameters in the overall group. Only the ER/PR?,Her2? subgroup showed a significant positive correlation between FDG and RGD PET parameters (r?=?0.59, p?=?0.03 for SUV_max).

Conclusion

⁶⁸Ga-RGD and ¹⁸F-FDG PET/CT are promising functional imaging modalities for predicting biomarkers and molecular phenotypes in breast cancer patients.     

Prospective evaluation of solitary thyroid nodule on 18F-FDG PET/CT and high-resolution ultrasonography

Purpose

The utility of 18F-FDG PET/CT in the assessment of thyroid nodules is unclear as there are several conflicting reports on the usefulness of SUV as an indicator to distinguish benign from malignant thyroid lesions. This study incorporated an additional parameter, namely dual time point imaging, to determine the diagnostic accuracy of PET/CT imaging. The performance of 18F-FDG PET/CT was compared to that of high-resolution ultrasound which is routinely used for the evaluation of thyroid nodules.

Methods

Two hundred patients with incidentally detected solitary thyroid nodules were included in the study. Each patient underwent ultrasound and PET/CT evaluation within 7 days of each other, reported by an experienced radiologist and nuclear medicine specialist, respectively, in a blinded manner. The PET/CT criteria employed were maximum SUV (SUV_max) at 60 min and change in SUV_max at delayed (120 min) imaging. Final diagnosis was based on pathological evaluation and follow-up.

Results

Of the 200 patients, 26 had malignant and 174 had benign nodules. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of ultrasound were 80.8, 81.6, 39.6, 96.6 and 81.5%, respectively. Using SUV_max at 60 min as the diagnostic criterion, the above indices were 80.8, 84.5, 43.8, 96.7 and 84%, respectively, for PET/CT. The SUV_max of malignant thyroid lesions was significantly higher than benign lesions (16.2 ± 10.6 vs. 4.5 ± 3.1, respectively; p = 0.0001). Incorporation of percentage change in SUV_max at delayed imaging as the diagnostic criterion yielded a slightly improved sensitivity, specificity, PPV, NPV and accuracy of 84.6, 85.6, 46.8, 97.4 and 85.5%, respectively. There was a significant difference in percentage change in SUV_max between malignant and benign thyroid lesions (14.9 ± 11.4 vs. ?1.6 ± 13.7, respectively; p = 0.0001). However, there was no statistically significant difference (95% confidence interval) between the diagnostic performance of PET/CT and ultrasound.

Conclusions

Routine use of 18F-FDG PET/CT with SUV_max at 60 min as the sole diagnostic criterion does not appear to have a significant advantage over high-resolution ultrasound in the evaluation of thyroid nodules. Incorporation of dual time point imaging enhances image interpretation, and yields a higher diagnostic performance, yet it is not statistically significant. Bearing in mind the cost, limited availability and radiation exposure, routine use of 18F-FDG PET/CT for distinguishing benign from malignant thyroid nodules cannot be recommended.     

Preoperative PET/CT FDG standardized uptake value of pelvic lymph nodes as a significant prognostic factor in patients with uterine cervical cancer

Purpose

Using integrated PET/CT, we evaluated the prognostic relevance in uterine cervical cancer of preoperative pelvic lymph node (LN) [¹⁸F]FDG uptake.

Methods

Patients with FIGO stage IB to IIA uterine cervical cancer were imaged with FDG PET/CT before radical surgery. We used Cox proportional hazards regression to examine the relationship between recurrence and the FDG maximum standardized uptake value (SUV_max) in the pelvic LN (SUV_LN) on PET/CT.

Results

Clinical data, treatment modalities, and results in 130 eligible patients were reviewed. The median postsurgical follow-up was 34 months (range 6 to 109 months). Receiver operating characteristic analysis identified SUV_LN 2.36 as the most significant cut-off value for predicting recurrence. SUV_LN was correlated with SUV_tumour (P?=?0.002), primary tumour size (P?=?0.004), and parametrial invasion (P?=?0.013). Univariate analyses showed significant associations between recurrence and SUV_LN (P?=?0.001), SUV_tumour (P?=?0.007), pelvic LN metastasis (P?=?0.002), parametrial invasion (P?<?0.001), primary tumour size (P?=?0.007), suspected LN metastasis on MRI (P?=?0.024), and FIGO stage (P?=?0.026). Multivariate analysis identified SUV_LN (P?=?0.013, hazard ratio, HR, 4.447, 95 % confidence interval, CI, 1.379 – 14.343) and parametrial invasion (P?=?0.013, HR 6.728, 95 % CI 1.497 – 30.235) as independent risk factors for recurrence. Patients with SUV_LN ≥2.36 and SUV_LN <2.36 differed significantly in terms of recurrence (HR 15.20, P?<?0.001).

Conclusion

Preoperative pelvic LN FDG uptake showed a strong significant association with uterine cervical cancer recurrence.     

<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.

     

18F-FAMT in patients with multiple myeloma: clinical utility compared to 18F-FDG

Objective

l-[3-¹⁸F]-alpha-methyltyrosine (¹⁸F-FAMT) is an amino-acid tracer for positron emission tomography (PET), with uptake related to overexpression of L-type amino-acid transporter 1 and proliferative activity in tumour cells. This study evaluated the diagnostic performance of ¹⁸F-FAMT PET compared with 2-[¹⁸F]-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) PET in patients with multiple myeloma (MM).

Methods

Eleven patients with MM (newly diagnosed, n?=?3; relapsed after treatment, n?=?8) underwent whole-body ¹⁸F-FAMT and ¹⁸F-FDG PET within a 2-week interval. Magnetic resonance imaging (MRI) of the spine was also performed to assess patterns of bone marrow infiltration. Tracer uptake was semi-quantitatively evaluated using maximal standardized uptake value (SUV_max). Mean SUV was also determined for normal bone marrow and the aortic arch as mediastinal background SUV to calculate lesion-to-bone marrow (L/B) and lesion-to-mediastinum (L/M) ratios, respectively. Those values were statistically compared using Student??s t test.

Results

In 8 patients showing focal infiltration on MRI, 34 FDG-avid bone lesions were identified, with each showing increased FAMT uptake. Mean SUV_max and L/B ratio of FDG (3.1?±?1.2 and 3.3?±?1.9, respectively) were significantly higher than those of FAMT (2.0?±?1.0 and 2.6?±?1.1, respectively; p?<?0.05 each). In contrast, the L/M ratio of FDG showed no significant difference to that of FAMT (2.2?±?1.0 and 2.4?±?1.2, respectively; p?=?0.3).

Conclusions

Clear ¹⁸F-FAMT PET uptake was seen in most ¹⁸F-FDG-avid lesions among patients with MM, and an equivalent semi-quantitative value was obtained using L/M ratio. Our preliminary data suggest that ¹⁸F-FAMT PET provides a useful imaging modality for detecting active myelomatous lesions.     

18F-FDG uptake as a prognostic variable in primary differentiated thyroid cancer incidentally detected by PET/CT: a multicentre study

Purpose

Our aim was to investigate the association between ¹⁸F-fluorodeoxyglucose (FDG) uptake and event-free survival in patients in whom a differentiated thyroid cancer (DTC) was detected by ¹⁸F-FDG positron emission tomography (PET)/CT.

Methods

Among 884 focal ¹⁸F-FDG PET thyroid incidentalomas referred to our 4 Nuclear Medicine Departments, we investigated 54 patients in whom a DTC was confirmed and a clinical follow-up was available. The ratio between maximum standardized uptake value (SUV_max) of DTC and SUV_mean of the liver (SUV ratio) was recorded for each scan. All patients underwent total thyroidectomy and ¹³¹I remnant ablation. After a median follow-up of 39 months we assessed the outcome. The association between disease persistence/progression, ¹⁸F-FDG uptake and other risk factors (T, N, M and histological subtype) was evaluated through univariate and multivariate analyses.

Results

Of the 54 patients, 39 achieved complete remission. The remaining 15 showed persistence/progression of disease. High ¹⁸F-FDG uptake, i.e. SUV ratio ≥3, showed a low positive predictive value (48 %). Low ¹⁸F-FDG uptake (SUV ratio?<?3) displayed a high negative predictive value (93 %). The median of SUV ratios in T1–T2 (2.2), in M0 (2.7) and in non-virulent subtypes (2.7) were significantly lower (p?<?0.03) than in T3–T4 (5.0), M1 (7.3) and virulent subtypes (6.0). Kaplan-Maier analysis showed a significant association between high ¹⁸F-FDG uptake and disease persistence/progression (p?=?0.001). When we adjusted risk estimates by using a multivariate Cox model, only T (p?=?0.05) remained independently associated with disease persistence/progression.

Conclusion

An intense ¹⁸F-FDG uptake of the primary DTC is associated with persistence/progression of disease. However, when all other prognostic factors have been taken into account, ¹⁸F-FDG uptake does not add further prognostic information.