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.     

Suppression of myocardial 18F-FDG uptake with a preparatory “Atkins-style” low-carbohydrate diet

Objectives

Physiological myocardial uptake of 18F-FDG during positron emission tomography can mask adjacent abnormal uptake in mediastinal malignancy and inflammatory cardiac diseases. Myocardial uptake is unpredictable and variable. This study evaluates the impact of a low-carbohydrate diet in reducing myocardial FDG uptake.

Method

Patients attending for clinically indicated oncological FDG PET were asked to have an “Atkins-style” low-carbohydrate diet (less than 3 g) the day before examination and an overnight fast. A total of 120 patients following low-carbohydrate diet plus overnight fast were compared with 120 patients prepared by overnight fast alone. Patients having an Atkins-style diet also completed a diet compliance questionnaire. SUV_max and SUV_mean for myocardium, blood pool and liver were measured in both groups.

Results

Myocardial SUV_max fell from 3.53?±?2.91 in controls to 1.77?±?0.91 in the diet-compliant group. 98 % of diet-compliant patients had a myocardial SUV_max less than 3.6 compared with 67 % of controls. Liver and blood pool SUV_max rose from 2.68?±?0.49 and 1.82?±?0.30 in the control group to 3.14?±?0.57 and 2.06?±?0.30.

Conclusion

An Atkins-style diet the day before PET, together with an overnight fast, effectively suppresses myocardial FDG uptake.

Key Points

? Low-carbohydrate diet (LCD) the day before PET suppresses myocardial FDG uptake. ? LCD before PET increases liver and blood pool SUV _max and SUV _mean . ? Suppression of myocardial uptake may improve PET imaging of thoracic disease. ? Suppression of myocardial uptake may help imaging cardiac inflammatory disease with PET.     

Inferior glucose metabolism and chemosensitivity of post-radiotherapy local recurrence in comparison with distant metastases as assessed by sequential 18F-FDG PET/CT imaging

Purpose

To compare glucose metabolism and chemosensitivity between recurrence within the irradiation field and metastases outside the irradiation field in the same patient using ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography images (PET/CT).

Methods

The ¹⁸F-FDG PET/CT images of 43 cancer patients with both local recurrence (in-field) and distal metastases (out-field) after initial treatments were reviewed. 23 patients after definitive radiotherapy/chemoradiotherapy and 20 patients after radical surgery were assigned to a radiation group and surgery group, respectively. The tumor maximal diameter on CT and PET images (D _CT and D _PET), maximal SUV (SUV_max), and mean SUV (SUV_mean) were measured. All the patients were administered chemotherapy, and 17 patients from the radiation group and 10 patients from the surgery group underwent PET/CT scanning within 1–2 months after the treatment. The changes in D _CT, D _PET, SUV_max and SUV_mean for each lesion were calculated and compared between in-field and out-field tumors for both groups.

Results

In the surgery group, no significant difference was found in tumor size or FDG uptake between the local recurrence and metastases. In the radiation group, both SUV_max (7.03 ± 3.48) and SUV_mean (4.33 ± 1.67) of the in-field tumors were lower than those (8.45 ± 4.34 and 5.36 ± 2.51, respectively, P < 0.05) of out-field tumors. Moreover, the response extent of in-field tumors was lower than that of out-field tumors in the radiation group (P < 0.05). However, in the surgery group, there was no difference in the response extent (tumor size and SUVs) between the local recurrence and metastases (P > 0.05).

Conclusion

The recurrence within the irradiation field and metastases outside the irradiation field in the same patient do not share the same biological characteristics or treatment response, with inferior glucose metabolism and chemosensitivity seen in locally recurrent tumors.     

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.     

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.     

Metabolic parameters using 18F-FDG PET/CT correlate with occult lymph node metastasis in squamous cell lung carcinoma

Purpose

The aim of this study was to investigate predictability of occult lymph node metastasis (OLM) using metabolic parameters on pretreatment ¹⁸F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/CT in squamous cell non-small cell lung carcinoma (SC-NSCLC) patients who were clinically node negative (cN0) before surgery.

Methods

A total of 63 cN0 SC-NSCLC patients (M/F = 61/2, mean age 64.1?±?8.0) who underwent curative surgery with lymph node dissection were enrolled in this study. Metabolic tumor volume (MTV) of the primary tumor was obtained with a standardized uptake value (SUV) threshold of 2.5. Total lesion glycolysis (TLG) was calculated by multiplication of the MTV and its SUV_mean. Metabolic parameters (SUV_max, MTV, and TLG) and clinicopathological factors were analyzed for OLM.

Results

Of 63 patients, 12 (19.0 %) had OLM. Significantly higher SUV_max, MTV, TLG, and pathological tumor size were observed in patients with OLM. The optimal cutoff values for prediction of OLM determined using a receiver-operating characteristic (ROC) curve were 8.8 for SUV_max, 18.9 cm³ for MTV, 88.4 for TLG, and 2.8 cm for pathological tumor size. Univariate analysis showed correlation of SUV_max, MTV, and TLG with the rate of OLM. In multivariate analyses, high SUV_max and MTV showed an association with an increased risk of OLM, after adjusting for age, sex, pathological tumor size, T stage, and location.

Conclusion

Metabolic parameters on pretreatment ¹⁸F-FDG PET/CT were significant predictors for OLM in cN0 SC-NSCLC patients. Surgical planning can be tailored based on the parameters in order to reduce the risk of hidden residual lymph node metastases in patients.     

Pulmonary <Superscript>18</Superscript>F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF)

Purpose

There is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of ¹⁸F-FDG-PET/ CT to predict mortality in IPF.

Methods

A total of 113 IPF patients (93 males, 20 females, mean age?±?SD: 70?±?9 years) were prospectively recruited for ¹⁸F-FDG-PET/CT. The overall maximum pulmonary uptake of ¹⁸F-FDG (SUV_max), the minimum pulmonary uptake or background lung activity (SUV_min), and target-to-background (SUV_max/ SUV_min) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan–Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary ¹⁸F-FDG-PET measurements and GAP score for risk stratification in IPF patients.

Results

During a mean follow-up of 29 months, there were 54 deaths. The mean TBR?±?SD was 5.6?±?2.7. Mortality was associated with high pulmonary TBR (p?=?0.009), low forced vital capacity (FVC; p?=?0.001), low transfer factor (TLCO; p?<?0.001), high GAP index (p?=?0.003), and high GAP stage (p?=?0.003). Stepwise forward-Wald–Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p?=?0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR?> 4.9 was 24 months. Combining PET data with GAP data (“PET modified GAP score”) refined the ability to predict mortality.

Conclusions

A high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.

     

18F-FDG PET-CT uptake is a feature of both normal diameter and aneurysmal aortic wall and is not related to aneurysm size

Purpose

Aortic metabolic activity is suggested to correlate with presence and progression of aneurysmal disease, but has been inadequately studied. This study investigates the 2-[¹⁸F] fluoro-2-deoxy-D-glucose (¹⁸F-FDG) uptake in a population of infra-renal abdominal aortic aneurysms (AAA), compared to a matched non-aneurysmal control group.

Methods

The Positron Emission Tomography – Computed Tomography (PET/CT) database was searched for infra-renal AAA. Exclusion criteria were prior repair, vasculitis, and saccular/mycotic thoracic or thoraco-abdominal aneurysms. Matching of 159 non-aneurysmal (<3 cm diameter) controls from the same population was assessed. Infra-renal aortic wall FDG uptake was assessed using visual analysis; maximum standardized uptake value (SUV_max) and target to background mediastinal blood pool ratio (TBR) were documented. Predictors of FDG uptake (age, sex, aortic diameter, hypertension, statin use, and diabetes) were assessed using univariate analysis. Follow-up questionnaires were sent to referring clinicians.

Results

Aneurysms (n?=?151) and controls (n?=?159) were matched (p?>?0.05) for age, sex, diabetes, hypertension, smoking status, statin use, and indication for PET/CT. Median aneurysm diameter was 5.0 cm (range 3.2–10.4). On visual analysis there was no significant difference in the overall numbers with increased visual uptake 24 % (36/151) in the aneurysm group vs. 19 % (30/159) in the controls, p?=?ns. SUV_max was slightly lower in the aneurysm group vs. controls (mean (2 SD) 1.75(0.79) vs. 1.84(0.58), p?=?0.02). However there was no difference in TBR between the AAA group and controls (mean (2 SD) 1.03 (0.46) vs. 1.05(0.31), p?=?0.36). During a median 18 (interquartile range 8–35) months’ follow-up 20 were repaired and four were confirmed ruptured.

Conclusions

The level of metabolic activity as assessed by ¹⁸F-FDG PET/CT in infra-renal AAA does not correlate with aortic size and does not differ between aneurysms and matched controls.     

Incidental pituitary uptake on whole-body 18F-FDG PET/CT: a multicentre study

Purpose

The purpose of this study was to determine the incidence of incidental pituitary uptake on whole-body ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and to investigate its clinical significance.

Methods

The files of 40,967 patients who underwent whole-body FDG PET/CT were retrospectively reviewed. Quantification of pituitary metabolic activity was obtained by using the maximum standardized uptake value (SUV_max). Hormone assays and pituitary MRIs were performed to assess pituitary lesions.

Results

Focally increased pituitary FDG uptake on PET/CT was found in 30 of 40,967 patients, accounting for an incidence of 0.073%. The mean SUV_max of 30 patients was 8.9?±?6.6 (range: 3.2–32.6). Histological diagnosis was obtained in three patients and included two growth hormone-secreting adenomas and one non-functioning adenoma. Hormone assays were performed on serum samples from 11 patients, 2 of whom were shown to have hypersecretion of pituitary hormone. MRI was performed on 19 patients. Abnormal MRI findings suggesting a pituitary mass were found in 18 of 19 cases (94.7%). The mean SUV_max calculated without correction for partial volume effect for macroadenomas was significantly higher than the SUV_max for microadenomas (11.5?±?8.4 vs 4.8?±?1.3; p?<?0.05). There were no cases diagnosed with metastasis to the pituitary gland during clinical follow-up.

Conclusion

Incidental pituitary FDG uptake was a very rare finding. Cases with incidental pituitary FDG uptake were diagnosed primarily with clinically non-functioning adenomas, and there were also a few functioning adenomas. Further evaluations, including hormone assays and pituitary MRI, are warranted when pituitary uptake is found on FDG PET/CT.     

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.     

Correlation of FDG PET/CT Findings with Long-Term Growth and Clinical Course of Abdominal Aortic Aneurysm

Purpose

Herein, we report characteristics of ¹⁸F–fluorodeoxyglucose (FDG) uptake in abdominal aortic aneurysms (AAAs) during a long-term follow-up. In addition, we investigated the association between FDG uptake and the physician decision to perform an intervention.

Methods

We performed a retrospective review of 42 patients with AAAs who underwent FDG positron emission tomography (PET)/computed tomography (CT). The size of the AAA was measured in serial CT or PET/CT images. The long-term growth rate of AAAs was calculated by linear regression of the size change. Maximal SUV of the AAA (SUV_AAA) and mean SUV of the blood pool (SUV_Blood) were measured in PET/CT fusion images. To assess the FDG uptake of AAAs, the target-to-background ratio (TBR) was defined as the ratio of SUV_AAA to SUV_Blood. We compared FDG uptake of AAAs with the long-term growth rate of AAAs and clinical data.

Results

TBR was not significantly different between patients with and without significant growth (1.55 ± 0.20 vs. 1.57 ± 0.14; P = 0.5599). However, in patients with significant growth, TBR exhibited a significant positive correlation with the growth rate (r ²  = 0.2601, P = 0.0306). TBR also exhibited a significant difference between patients with and without intervention (P = 0.0228).

Conclusion

FDG uptake of AAA is associated with long-term growth of AAAs in a specified group that exhibits growth. FDG PET/CT may only be effective in predicting the long-term growth of AAAs in specific subgroups of patients. It is also suggested that FDG PET is potentially related to the clinical conditions of AAA patients who need surgical or interventional treatment.

     

[<Superscript>18</Superscript>F]FPRGD<Subscript>2</Subscript> PET/CT imaging of integrin α<Subscript>v</Subscript>β<Subscript>3</Subscript> levels in patients with locally advanced rectal carcinoma

Purpose

Our primary objective was to determine if [¹⁸F]FPRGD₂ PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC). Secondary objectives were to compare baseline [¹⁸F]FPRGD₂ and [¹⁸F]FDG uptake, to evaluate the correlation between posttreatment [¹⁸F]FPRGD₂ uptake and tumour microvessel density (MVD) and to determine if [¹⁸F]FPRGD₂ and FDG PET/CT could predict disease-free survival.

Methods

Baseline [¹⁸F]FPRGD₂ and FDG PET/CT were performed in 32 consecutive patients (23 men, 9 women; mean age 63?±?8 years) with LARC before starting any therapy. A posttreatment [¹⁸F]FPRGD₂ PET/CT scan was performed in 24 patients after the end of CRT (median interval 7 weeks, range 3 – 15 weeks) and before surgery (median interval 4 days, range 1 – 15 days).

Results

All LARC showed uptake of both [¹⁸F]FPRGD₂ (SUV_max 5.4?±?1.5, range 2.7 – 9) and FDG (SUV_max 16.5?±?8, range 7.1 – 36.5). There was a moderate positive correlation between [¹⁸F]FPRGD₂ and FDG SUV_max (Pearson’s r?=?0.49, p?=?0.0026). There was a moderate negative correlation between baseline [¹⁸F]FPRGD₂ SUV_max and the TRG (Spearman’s r?=??0.37, p?=?0.037), and a [¹⁸F]FPRGD₂ SUV_max of >5.6 identified all patients with a complete response (TRG 0; AUC 0.84, 95 % CI 0.68 - 1, p?=?0.029). In the 24 patients who underwent a posttreatment [¹⁸F]FPRGD₂ PET/CT scan the response index, calculated as [(SUV_max1 ? SUV_max2)/SUV_max1] × 100 %, was not associated with TRG. Post-treatment [¹⁸F]FPRGD₂ uptake was not correlated with tumour MVD. Neither [¹⁸F]FPRGD₂ nor FDG uptake predicted disease-free survival.

Conclusion

Baseline [¹⁸F]FPRGD₂ uptake was correlated with the pathological response in patients with LARC treated with CRT. However, the specificity was too low to consider its clinical routine use.

     

Functional imaging of head and neck squamous cell carcinoma with diffusion-weighted MRI and FDG PET/CT: quantitative analysis of ADC and SUV

Purpose

Head and neck squamous cell carcinoma (HNSCC) may cause a decreased apparent diffusion coefficient (ADC) on diffusion-weighted magnetic resonance imaging (DW MRI) and an increased standardized uptake value (SUV) on fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). We analysed the reproducibility of ADC and SUV measurements in HNSCC and evaluated whether these biomarkers are correlated or independent.

Methods

This retrospective analysis of DW MRI and FDG PET/CT data series included 34 HNSCC in 33 consecutive patients. Two experienced readers measured tumour ADC and SUV values independently. Statistical comparison and correlation with histopathology was done. Intra- and inter-observer agreement for ADC and SUV measurements was assessed.

Results

Intraclass correlation coefficient (ICC) analysis showed almost perfect reproducibility (>0.90) for ADC_mean, ADC_min, SUV_max and SUV_mean values for intra-observer and inter-observer agreement. Mean ADC_mean and ADC_min in HNSCC were 1.05?±?0.34 × 10^?3?mm²/s and 0.65?±?0.29 × 10^?3?mm²/s, respectively. Mean SUV_mean and mean SUV_max were 7.61?±?3.87 and 12.8?±?5.0, respectively. Although statistically not significant, a trend towards higher SUV and lower ADC was observed with increasing tumour dedifferentiation. Pearson’s correlation analysis showed no significant correlation between ADC and SUV measurements (r ?0.103, ?0.051; p 0.552, 0.777).

Conclusion

Our data suggest that ADC and SUV values are reproducible and independent biomarkers in HNSCC.     

[18F]Fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing αvβ3 and αvβ5 integrins

Purpose

[¹⁸F]Fluciclatide is an integrin-targeted PET radiopharmaceutical. α_vβ₃ and α_vβ₅ are upregulated in tumor angiogenesis as well as on some tumor cell surfaces. Our aim was to use [¹⁸F]fluciclatide (formerly known as [¹⁸F]AH111585) for PET imaging of angiogenesis in melanoma and renal tumors and compare with tumor integrin expression.

Methods

Eighteen evaluable patients with solid tumors ≥2.0 cm underwent [¹⁸F]fluciclatide PET/CT. All patients underwent surgery and tumor tissue samples were obtained. Immunohistochemical (IHC) staining with mouse monoclonal antibodies and diaminobenzidine (DAB) was applied to snap-frozen tumor specimens, and additional IHC was done on formalin-fixed paraffin-embedded samples. DAB optical density (OD) data from digitized whole-tissue sections were compared with PET SUV_{80% max}, and Patlak influx rate constant (K _i) data, tumor by tumor.

Results

Tumors from all 18 patients demonstrated measurable [¹⁸F]fluciclatide uptake. At the final dynamic time-point (55 min after injection), renal malignancies (in 11 patients) demonstrated an average SUV_{80% max} of 6.4?±?2.0 (range 3.8 – 10.0), while the average SUV_{80% max} for metastatic melanoma lesions (in 6 patients) was 3.0?±?2.0 (range 0.7 – 6.5). There was a statistically significant difference in [¹⁸F]fluciclatide uptake between chromophobe and nonchromophobe renal cell carcinoma (RCCs, with SUV_{80% max} of 8.2?±?1.8 and 5.4?±?1.4 (P?=?0.020) and tumor-to-normal kidney (T/N) ratios of 1.5?±?0.4 and 0.9?±?0.2, respectively (P?=?0.029). The highest Pearson's correlation coefficients were obtained when comparing Patlak K _i and α_vβ₅ OD when segregating the patient population between melanoma and RCC (r?=?0.83 for K _i vs. melanoma and r?=?0.91 for K _i vs. RCC). SUV_{80% max} showed a moderate correlation with α_vβ₅ and α_vβ₃ OD.

Conclusion

[¹⁸F]Fluciclatide PET imaging was well tolerated and demonstrated favorable characteristics for imaging α_vβ₃ and α_vβ₅ expression in melanoma and RCC. Higher uptake was observed in chromophobe than in nonchromophobe RCC. [¹⁸F]Fluciclatide may be a useful radiotracer to improve knowledge of integrin expression.     

68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

Purpose

We wanted to establish the range of ⁶⁸Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT).

Methods

In 249 patients, 390 ⁶⁸Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies).

Results

SUV_max (mean ± standard deviation) values of ⁶⁸Ga-DOTA-TOC were 29.8?±?16.5 in 162 liver metastases, 19.8?±?18.8 in 89 bone metastases and 34.6?±?17.1 in 43 pancreatic NET (33.6?±?14.3 in 30 tumours of the uncinate process and 36.3?±?21.5 in 13 tumours of the pancreatic tail). A significant difference in SUV_max (p?<?0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUV_max between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p?<?0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUV_max for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p?<?0.0001).

Conclusion

⁶⁸Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUV_max can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUV_max, except in liver metastases of patients with NET.     

Detection of internal mammary lymph node metastasis with 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with stage III breast cancer

Purpose

The present study assessed the positive predictive value (PPV) of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the detection of internal mammary node (IMN) metastasis in patients with clinical stage III breast cancer.

Methods

Patients who were diagnosed with clinical stage III breast cancer and underwent pretreatment ¹⁸F-FDG PET/CT were retrospectively analyzed. The ¹⁸F-FDG PET/CT scans were prospectively reviewed by two board-certified nuclear medicine physicians in a blinded manner. The intensities of IMNs were graded into four categories (no activity and lower, similar, and higher activities than that of the mediastinal blood pool). IMNs were measured from the combined CT (largest diameter of the short axis). Histologic data of the IMNs were obtained by ultrasonography-guided fine-needle aspiration biopsy or surgical excision. The PPV was calculated for pathologically confirmed IMNs. Visual grade, maximum standardized uptake values (SUV_max), and sizes were analyzed according to the pathology results.

Results

There were 249 clinical stage III breast cancer patients (age 48.0?±?10.1 years, range 26–79 years) who had undergone initial ¹⁸F-FDG PET/CT prior to treatment. Excluding 33 cases of stage IV breast cancer, 62 of 216 patients had visible IMNs on ¹⁸F-FDG PET/CT, and histologic confirmation was obtained in 31 patients. There were 27 metastatic and four nonmetastatic nodes (PPV 87.1 %). Metastatic nodes mostly presented with visual grade 3 (83.9 %), and SUV_max and size were 3.5?±?4.3 and 5.6?±?2.0 mm, respectively.

Conclusion

¹⁸F-FDG PET/CT has a high PPV for IMN metastasis in clinical stage III breast cancer, indicating the possibility of metastasis in IMNs with FDG uptake similar to/lower than that of the blood pool or small-sized nodes.     

Detection of unknown primary neuroendocrine tumours (CUP-NET) using 68Ga-DOTA-NOC receptor PET/CT

Purpose

This bi-centric study aimed to determine the role of receptor PET/CT using ⁶⁸Ga-DOTA-NOC in the detection of undiagnosed primary sites of neuroendocrine tumours (NETs) and to understand the molecular behaviour of the primarily undiagnosed tumours.

Methods

Overall 59 patients (33 men and 26 women, age: 65?±?9 years) with documented NET and unknown primary were enrolled. PET/CT was performed after injection of approximately 100 MBq (46–260 MBq) of ⁶⁸Ga-DOTA-NOC. The maximum standardised uptake values (SUV_max) were calculated and compared with SUV_max in known pancreatic NET (pNET) and ileum/jejunum/duodenum (SI-NET). The results of PET/CT were also correlated with CT alone.

Results

In 35 of 59 patients (59%), ⁶⁸Ga-DOTA-NOC PET/CT localised the site of the primary: ileum/jejunum (14), pancreas (16), rectum/colon (2), lungs (2) and paraganglioma (1). CT alone (on retrospective analyses) confirmed the findings in 12 of 59 patients (20%). The mean SUV_max of identified previously unknown pNET and SI-NET were 18.6?±?9.8 (range: 7.8–34.8) and 9.1?±?6.0 (range: 4.2–27.8), respectively. SUV_max in patients with previously known pNET and SI-NET were 26.1?±?14.5 (range: 8.7–42.4) and 11.3?±?3.7 (range: 5.6–17.9). The SUV_max of the unknown pNET and SI-NET were significantly lower (p?<?0.05) as compared to the ones with known primary tumour sites; 19% of the patients had high-grade and 81% low-grade NET. Based on ⁶⁸Ga-DOTA-NOC receptor PET/CT, 6 of 59 patients were operated and the primary was removed (4 pancreatic, 1 ileal and 1 rectal tumour) resulting in a management change in approximately 10% of the patients. In the remaining 29 patients, because of the far advanced stage of the disease (due to distant metastases), the primary tumours were not operated. Additional histopathological sampling was available from one patient with bronchial carcinoid (through bronchoscopy).

Conclusion

Our data indicate that ⁶⁸Ga-DOTA-NOC PET/CT is highly superior to ¹¹¹In-OctreoScan (39% detection rate for CUP according to the literature) and can play a major role in the management of patients with CUP-NET.     

What parameters from 18F-FDG PET/CT are useful in evaluation of adrenal lesions?

Purpose

Prior studies have suggested that ¹⁸F-FDG PET/CT can help characterize adrenal lesions and differentiate adrenal metastases from benign lesions. The aim of this study was to assess the value of ¹⁸F-FDG PET/CT for the differentiation of malignant from benign adrenal lesions.

Methods

This retrospective study included 85 patients (47 men and 38 women, age 63.8?±?10.8 years) who had undergone ¹⁸F-FDG PET/CT (60 min after injection 300 – 370 MBq ¹⁸F-FDG; Biograph 64 scanner) for evaluation of 102 nonsecreting adrenal masses. For semiquantitative analysis, the maximum standardized uptake value (SUVmax), adrenal to liver (T/L) SUVmax ratio, mean CT attenuation value and tumour diameter were measured in all lesions and compared with the pathological findings.

Results

Malignant adrenal tumours (68 % of evaluated tumours) had a significantly higher mean SUVmax (13.0?±?7.1 vs. 3.7?±?3.0), a higher T/L SUVmax ratio (4.2?±?2.6 vs. 1.0?±?0.9), a higher CT attenuation value (31.9?±?16. 7 HU vs. 0.2?±?25.8 HU) and a greater diameter (43.6?±?23.7 mm vs. 25.6?±?13.3 mm) than benign lesions. The false-positive findings were tuberculosis and benign phaeochromocytoma. Based on ROC analysis, a T/L SUVmax ratio >1.53, an adrenal SUVmax >5.2, an attenuation value >24 HU and a tumour diameter >30 mm were chosen as the optimal cut-off values for differentiating malignant from benign tumours. The areas under the ROC curves for the selected cut-off values were 0.96, 0.96, 0.88 and 0.77, respectively. A multivariate logistic regression model revealed that the T/L SUVmax ratio was an independent prognostic factor for malignancy (p?25 HU and a tumour diameter >30 mm had no additional individual importance in the diagnosis of malignancy.

Conclusion

Using a T/L SUVmax ratio >1.53 and an adrenal SUVmax >5.2 in ¹⁸F-FDG PET/CT led to high diagnostic sensitivity, specificity and negative predictive value for characterizing adrenal tumours. The diagnostic accuracies of the two parameters were comparable, but T/L SUVmax ratio was an independent predictor of malignancy.     

Repeatability of hypoxia PET imaging using [<Superscript>18</Superscript>F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Purpose

Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [¹⁸F]HX4 in patients with head and neck and lung cancer.

Methods

Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [¹⁸F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUV_max and SUV_mean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV_1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.

Results

All parameters of [¹⁸F]HX4 uptake were significantly correlated between scans: SUV_max (r?=?0.958, p?<?0.001), SUV_mean (r?=?0.946, p?<?0.001), TBR_max (r?=?0.962, p?<?0.001) and HV_1.2 (r?=?0.995, p?<?0.001). The relative coefficients of repeatability were 15 % (SUV_mean), 17 % (SUV_max) and 17 % (TBR_max). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65?±?0.14.

Conclusion

Repeated hypoxia PET scans with [¹⁸F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [¹⁸F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.

     

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.