Prognostic relevance of 18F-FDG PET uptake in patients with locally advanced,extremity soft tissue sarcomas undergoing neoadjuvant isolated limb perfusion with TNF-α and melphalan

Purpose

The objective of this study was to determine whether ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) can adequately assess the risk of systemic disease progression in patients with primary, localized, high-grade soft tissue sarcomas of the extremities undergoing neoadjuvant isolated limb perfusion (ILP) with tumour necrosis factor and melphalan.

Methods

This was a retrospective analysis of the files of 35 patients who underwent a PET or PET/CT scan prior to and after ILP followed by surgical resection with curative intent between 2006 and 2012. SUV_max1 was defined as the maximum standardized uptake value (SUV) at diagnosis, SUV_max2 as the maximum SUV after ILP and ΔSUV_max as the percentage difference between SUV_max1 and SUV_max2.

Results

The median follow-up was 40 months for all patients. The median SUV_max1 amounted to 7.6, while the median SUV_max2 was 4.7. The median ΔSUV_max was ?44 %. Overall survival (OS) probability at 2 and 5 years amounted to 78 and 70 %, respectively, while metastasis-free survival (MFS) probability at 2 and 5 years was 67 and 64 %, respectively. Receiver-operating characteristic (ROC) curve analysis showed that both SUV_max2 and ΔSUV_max could predict systemic disease progression, while SUV_max1 could not adequately identify patients who went on to develop metastatic disease. The optimal cut-off value was 6.9 for SUV_max2 and ?31 % for ΔSUV_max. Patients with an SUV_max2 <6.9 had a 2-year MFS of 80 %, compared to 31 % for patients with an SUV_max2?≥?6.9 (p?<?0.001). Patients with a ΔSUV_max?<??31 %, i.e. patients with a higher metabolic response, had an MFS of 76 % at 2 years, compared to 42 % for patients with a ΔSUV_max?≥??31 % (p?=?0.050).

Conclusion

SUV_max after ILP for primary, locally advanced, non-metastatic high-grade soft tissue sarcomas of the extremities appears to be significantly correlated with prognosis. Whether patients with a high SUV_max after ILP will benefit from standard or experimental adjuvant systemic treatment options should be evaluated in future studies.     

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.     

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.     

HER2-positive breast cancer: 18F-FDG PET for early prediction of response to trastuzumab plus taxane-based neoadjuvant chemotherapy

Purpose

To investigate the value of ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET/CT) to predict a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Material and methods

Fifty-seven consecutive women with HER2-positive breast cancer, treated with trastuzumab plus taxane-based NAC, were prospectively included. Maximum Standardized Uptake Value of the primary tumor and axillary nodes were measured at baseline (PET₁.SUV_max) and after the first course of NAC (PET₂.SUV_max). Tumor metabolic volumes were assessed to determine Total Lesion Glycolysis (TLG). The tumor metabolic response (ΔSUV_max and ΔTLG) was calculated.

Results

In univariate analysis, negative hormonal receptor status (p?=?0.04), high tumor grade (p?=?0.03), and low tumor PET ₂ .SUV_max (p?=?0.001) were predictive of pCR. Tumor ΔSUV_max correlated with pCR (p?=?0.03), provided that tumors with low metabolic activity at baseline were excluded. ΔTLG did not correlate with pCR. In multivariate analysis, tumor PET₂.SUV_max?<?2.1 was the best independent predictive factor (Odds ratio =14.3; p?=?0.004) with both negative and positive predictive values of 76 %. Although the metabolic features of the primary tumor did not depend on hormonal receptor status, both the baseline metabolism and early response of axillary nodes were higher if estrogen receptors were not expressed (p?=?0.01 and p?=?0.03, respectively).

Conclusion

In HER2-positive breast cancer, very low tumor residual metabolism after the first cycle of NAC (SUV_max?<?2.1) was the main predictor of pCR. These results should be further explored in multicenter studies and incorporated into the design of clinical trials.     

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 the PET component of simultaneous [18F]choline PET/MRI in prostate cancer: comparison with [18F]choline PET/CT

Purpose

The aim of this study was to evaluate the positron emission tomography (PET) component of [¹⁸F]choline PET/MRI and compare it with the PET component of [¹⁸F]choline PET/CT in patients with histologically proven prostate cancer and suspected recurrent prostate cancer.

Methods

Thirty-six patients were examined with simultaneous [¹⁸F]choline PET/MRI following combined [¹⁸F]choline PET/CT. Fifty-eight PET-positive lesions in PET/CT and PET/MRI were evaluated by measuring the maximum and mean standardized uptake values (SUV_max and SUV_mean) using volume of interest (VOI) analysis. A scoring system was applied to determine the quality of the PET images of both PET/CT and PET/MRI. Agreement between PET/CT and PET/MRI regarding SUV_max and SUV_mean was tested using Pearson’s product-moment correlation and Bland-Altman analysis.

Results

All PET-positive lesions that were visible on PET/CT were also detectable on PET/MRI. The quality of the PET images was comparable in both groups. Median SUV_max and SUV_mean of all lesions were significantly lower in PET/MRI than in PET/CT (5.2 vs 6.1, p?<?0.05 and 2.0 vs 2.6, p?<?0.001, respectively). Pearson’s product-moment correlation indicated highly significant correlations between SUV_max of PET/CT and PET/MRI (R?=?0.86, p?<?0.001) as well as between SUV_mean of PET/CT and PET/MRI (R?=?0.81, p?<?0.001). Bland-Altman analysis revealed lower and upper limits of agreement of ?2.77 to 3.64 between SUV_max of PET/CT vs PET/MRI and ?1.12 to +2.23 between SUV_mean of PET/CT vs PET/MRI.

Conclusion

PET image quality of PET/MRI was comparable to that of PET/CT. A highly significant correlation between SUV_max and SUV_mean was found. Both SUV_max and SUV_mean were significantly lower in [¹⁸F]choline PET/MRI than in [¹⁸F]choline PET/CT. Differences of SUV_max and SUV_mean might be caused by different techniques of attenuation correction. Furthermore, differences in biodistribution and biokinetics of [¹⁸F]choline between the subsequent examinations and in the respective organ systems have to be taken into account.     

Dual-time-point [18F]-FDG PET/CT in the diagnostic evaluation of suspicious breast lesions

Purpose

The authors sought to evaluate whether the reacquisition of images 3 h after administration of radiotracer improves the sensitivity of fluorine-18 fluorodeoxyglucose positron emission tomography computed tomography ([¹⁸F]-FDG PET/CT) in patients with suspicious breast lesions.

Materials and methods

Forty-eight patients with 59 breast lesions underwent an [¹⁸F]-FDG PET/CT study in the prone position with a dual-time-point acquisition performed in the early phase 1 h after FDG administration (PET-1) and in the delayed phase 3 h after FDG administration (PET-2). Both examinations were evaluated qualitatively and semiquantitatively with calculation of the mean percentage variation of the standard uptake values (Δ% SUV_max) between PET-1 and PET-2. All lesions with an SUV_max ≥2.5 at PET-1 or a reduction in SUV between PET-1 and PET-2 were considered benign. The definitive histopathological diagnosis was available for all patients included in the study.

Results

The dual-time-point acquisition of [¹⁸F]-FDG PET/CT displayed an accuracy of 85% for lesions with an SUV_max ≥2.5 and/or positive Δ% SUV_max, with sensitivity and specificity values of 81% and 100% compared with 69%, 63% (both p<0.001) and 100% (p=n.s.), respectively, for the single-time-point acquisition. Malignant lesions showed an increase in FDG uptake between PET-1 and PET-2, with a Δ% SUV_max of 10±7 (p<0.04). In contrast, benign lesions showed a decrease in SUV between PET-1 and PET-2, with aΔ% SUV_max of ?21±7 (p<0.001).

Conclusions

The delayed repeat acquisition of PET images improves the accuracy of [¹⁸F]-FDG PET/CT in patients with suspicious breast lesions with respect to the single-time-point acquisition. In addition, malignant breast lesions displayed an increase in FDG uptake over time, whereas benign lesions showed a reduction. These variations in FDG uptake between PET-1 and PET-2 are a reliable parameter that can be used for differentiating between benign and malignant breast lesions.     

FDG PET/CT in Crohn’s disease: correlation of quantitative FDG PET/CT parameters with clinical and endoscopic surrogate markers of disease activity

Purpose

The aim of this study was to determine the feasibility and potential clinical utility of assessment of Crohn’s disease (CD) activity by ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT employing a new quantitative approach.

Methods

A total of 22 subjects (mean age 37) with CD who had undergone FDG PET/CT followed by ileocolonoscopy within 1 week were included in this analysis. The CD endoscopy index of severity (CDEIS) for various bowel segments was calculated. The CD activity index (CDAI) was evaluated, and fecal calprotectin was measured. On PET, regions with increased FDG uptake in large bowel were segmented with an adaptive contrast-oriented thresholding algorithm, and metabolically active volume (MAV), uncorrected mean standardized uptake value (SUV_mean), partial volume-corrected SUV_mean (PVC-SUV_mean), SUV_max, uncorrected total lesion glycolysis (TLG = MAV × SUV_mean), and PVC total lesion glycolysis (PVC-TLG = MAV × PVC-SUV_mean) were measured. Global CD activity score (GCDAS) was calculated as the sum of PVC-TLG over all clinically significant FDG-avid regions in each subject. Correlations between regional PET quantification measures (SUVs, TLGs) and CDEIS were calculated. Correlations between the global PET quantification measure (GCDAS, global SUVs) with CDAI, fecal calprotectin, CDEIS, and CRP level were also calculated.

Results

SUV_max, PVC-SUV_mean, and PVC-TLG significantly correlated with segment CDEIS subscores (r?=?0.50, r?=?0.69, and r?=?0.31, respectively; p?<?0.05). GCDAS significantly correlated with CDAI and fecal calprotectin (r?=?0.64 and r?=?0.51, respectively; p?<?0.05).

Conclusion

By employing this new quantitative approach, we were able to calculate indices of regional and global CD activity, which correlated well with both clinical and pathological disease activity surrogate markers. This approach may be of clinical importance in measuring both global disease activity and treatment response in patients with CD.     

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.     

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.     

PET SUV correlates with radionuclide uptake in peptide receptor therapy in meningioma

Purpose

To investigate whether the tumour uptake of radionuclide in peptide receptor radionuclide therapy (PRRT) of meningioma can be predicted by a PET scan with ⁶⁸Ga-labelled somatostatin analogue.

Methods

In this pilot trial, 11 meningioma patients with a PET scan indicating somatostatin receptor expression received PRRT with 7.4?GBq ¹⁷⁷Lu-DOTATOC or ¹⁷⁷Lu-DOTATATE, followed by external beam radiotherapy. A second PET scan was scheduled for 3?months after therapy. During PRRT, multiple whole-body scans and a SPECT/CT scan of the head and neck region were acquired and used to determine the kinetics and dose in the voxel with the highest radionuclide uptake within the tumour. Maximum voxel dose and retention of activity 1?h after administration in PRRT were compared to the maximum standardized uptake values (SUV_max) in the meningiomas from the PET scans before and after therapy.

Results

The median SUV_max in the meningiomas was 13.7 (range 4.3 to 68.7), and the maximum fractional radionuclide uptake in voxels of size 0.11?cm3 was a median of 23.4?×?10^?6 (range 0.4?×?10^?6 to 68.3?×?10^?6). A strong correlation was observed between SUV_max and the PRRT radionuclide tumour retention in the voxels with the highest uptake (Spearman’s rank test, P?max and the therapeutic uptake (r?=?0.95) and between SUV_max and the maximum voxel dose from PRRT (r?=?0.76). Observed absolute deviations from the values expected from regression were a median of 5.6?×?10^?6 (maximum 9.3?×?10^?6) for the voxel fractional radionuclide uptake and 0.40?Gy per GBq (maximum 0.85?Gy per GBq) ¹⁷⁷Lu for the voxel dose from PRRT.

Conclusion

PET with ⁶⁸Ga-labelled somatostatin analogues allows the pretherapeutic assessment of tumour radionuclide uptake in PRRT of meningioma and an estimate of the achievable dose.     

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.     

Standardized added metabolic activity (SAM): a partial volume independent marker of total lesion glycolysis in liver metastases

Purpose

The standardized added metabolic activity (SAM) is a new marker of total lesion glycolysis that avoids partial volume effect (PVE) and thresholding. SAM is calculated by drawing a volume of interest (VOI₁) around the tumour and a larger VOI (VOI₂) around VOI₁. Subtracting the background activity in VOI₂-VOI₁ from VOI₁ yields SAM. If VOI₁ is set at a reasonable distance from the tumour, PVE are avoided. Phantom and initial clinical validation data are presented.

Methods

Spheres of a Jaszczak phantom were filled with a 5.4, 3.64 and 2.0 times higher concentration relative to background activity and positron emission tomography (PET) data were acquired during 10?min. SAM of all spheres was expressed as a percentage of the expected value (the actual activity ratio minus 1). In 15 patients a 10-min list-mode acquisition PET study centred on their primary squamous cell carcinoma (PSCC) was performed and images of 1-10?min reconstructed. SAM1-9min values of PSCC were expressed as a percentage of SAM10min. Nineteen patients suffering from liver metastases treated with chemotherapy underwent PET/CT prior to (scan 1) and after 3–6 cycles of chemotherapy (scan 2). SAM and maximum standardized uptake values (SUV_max) of the liver lesions on scan 1 (SAM1 and SUV_max1) and the percentage reduction between both ΔSAM and ΔSUV_max were related to Response Evaluation Criteria in Solid Tumors (RECIST) response.

Results

For the phantom acquisitions, the mean normalized SAM/sphere volume calculated was 94.9?% (SD 5.9?%) of the expected value. In the PSCC patients, the mean difference between SAM1min and SAM10min was only 4?% (SD 5?%). SUV_max1min and SUV_max10min proved to be not significantly different, but the variability was slightly larger than that of SAM (SD 6.4?%). SAM1 and ΔSAM values for responders versus non-responders were, respectively, 57 (SD 119) versus 297 (SD 625) for SAM1 (p?=?0.2) and 99?% (SD 3?%) versus 32?% (SD 44?%) for ΔSAM (p?=?0.001). SUV_max1 and ΔSUV_max values in responders versus non-responders were, respectively, 3.9 (SD 2.4) versus 6.3 (SD 3.1) for SUV_max1 (p?=?0.08) and 94?% (SD 17) versus 7?% (SD 40?%) for ΔSUV_max (p?=?0.0001). The AUC of ΔSAM and ΔSUV_max were not significantly different on receiver-operating characteristic (ROC) analysis (AUC 1.0 and 0.99, respectively, p?=?0.6).

Conclusion

SAM is a promising parameter for tumour response assessment of liver metastases by means of ¹⁸F-fluorodeoxyglucose PET.     

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.

     

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.     

[<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.

     

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.     

Heterogeneity of intrahepatic fat distribution determined by <Superscript>18</Superscript>F-FDG PET and CT

Objectives

Hepatic steatosis is common but less is known of the heterogeneity of hepatic fat distribution and its clinical significance. Our objective was to measure the regional variabilities within the liver of standardised uptake values (SUV) as potential markers of hepatic fat distribution heterogeneity.

Methods

Twenty-four patients having routine, clinically indicated PET/CT with ¹⁸F-FDG and a wide range of fatty liver severity were selected. Maximum SUV (SUV_max), average SUV (SUV_ave), both calculated using lean body mass, and CT density were measured in 12 × 2-cm diameter ROIs in each patient. SUV_ave was also measured over the left ventricular cavity (SUV_LV). Mean values of SUV indices, their ratios with SUV_LV, and CT density in the 12 ROIs were calculated. Regional variabilities of SUV indices were expressed as coefficients of variation (CV; standard deviation/mean). Body mass index (BMI) was estimated from height and body weight, and %body fat and lean body mass from height, weight and gender.

Results

Mean SUV_max/SUV_ave correlated significantly with mean CT density (r = ?0.51; p < 0.02). In contrast, mean SUV_max, mean SUV_ave and their ratios with SUV_LV showed no correlation with CT density. Mean CT density correlated with weight (r = ?0.59; p < 0.005), BMI (r = ?0.57; p < 0.01) and %body fat (r = ?0.49; p < 0.02). Corresponding correlation coefficients for mean SUV_max/SUV_ave were 0.74 (p < 0.001), 0.65 (p < 0.001) and 0.46 (p < 0.03). In contrast, mean SUV_max, mean SUV_ave and their ratios with SUV_LV showed no correlation with BMI, weight and %body fat. The CV of SUV_max/SUV_ave (r = ?0.67; p < 0.001), but not the CVs of SUV_max or SUV_ave, correlated with mean CT density.

Conclusions

SUV_max/SUV_ave and CT density are markers of hepatic steatosis. The regional variability of SUV_max/SUV_ave may be a marker of hepatic fat distribution heterogeneity. The novel concept is introduced that hepatic fat distribution heterogeneity may be a marker of hepatic pathology and of clinical value, and deserves further exploration with texture analysis.