Predictive value of pre-therapy 18F-FDG PET/CT for the outcome of 18F-FDG PET-guided radiotherapy in patients with head and neck cancer

Purpose

The aim of this study was to evaluate the predictive role of pre-therapy fluorodeoxyglucose (FDG) uptake parameters of primary tumour in head and neck cancer (HNC) patients undergoing intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) on FDG-positive volume—positron emission tomography (PET) gross tumour volume (PET-GTV).

Methods

This retrospective study included 19 patients (15 men and 4 women, mean age 59.2 years, range 23–81 years) diagnosed with HNC between 2005 and 2011. Of 19 patients, 15 (79 %) had stage III–IV. All patients underwent FDG PET/CT before treatment. Metabolic indexes of primary tumour, including metabolic tumour volume (MTV), maximum and mean standardized uptake value (SUV_max, SUV_mean) and total lesion glycolysis (TLG) were considered. Partial volume effect correction (PVC) was performed for SUV_mean and TLG estimation. Correlations between PET/CT parameters and 2-year disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were assessed. Median patient follow-up was 19.2 months (range 4–24 months).

Results

MTV, TLG and PVC-TLG predicting patients’ outcome with respect to all the considered local and distant disease control endpoints (LRFS, DMFS and DFS) were 32.4 cc, 469.8 g and 547.3 g, respectively. SUV_mean and PVC-SUV_mean cut-off values predictive of LRFS and DFS were 10.8 and 13.3, respectively. PVC was able to compensate errors up to 25 % in the primary HNC tumour uptake. Moreover, PVC enhanced the statistical significance of the results.

Conclusion

FDG PET/CT uptake parameters are predictors of patients’ outcome and can potentially identify patients with higher risk of treatment failure that could benefit from more aggressive approaches. Application of PVC is recommended for accurate measurement of PET parameters.     

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.

     

Reproducibility of functional volume and activity concentration in 18F-FDG PET/CT of liver metastases in colorectal cancer

Purpose

Several studies showed potential for monitoring response to systemic therapy in metastatic colorectal cancer patients with ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Before ¹⁸F-FDG PET can be implemented for response evaluation the repeatability should be known. This study was performed to assess the magnitude of the changes in standardized uptake value (SUV), volume and total lesion glycolysis (TLG) in colorectal liver metastases and validate the biological basis of ¹⁸F-FDG PET in colorectal liver metastases.

Methods

Twenty patients scheduled for liver metastasectomy underwent two ¹⁸F-FDG PET scans within 1?week. Bland-Altman analysis was performed to assess repeatability of SUV_max, SUV_mean, volume and TLG. Tumours were delineated using an adaptive threshold method (PET_SBR) and a semiautomatic fuzzy locally adaptive Bayesian (FLAB) delineation method.

Results

Coefficient of repeatability of SUV_max and SUV_mean were ～39 and ～31?%, respectively, independent of the delineation method used and image reconstruction parameters. However, repeatability was worse in recently treated patients. The FLAB delineation method improved the repeatability of the volume and TLG measurements compared to PET_SBR, from coefficients of repeatability of over 85?% to 45?% and 57?% for volume and TLG, respectively. Glucose transporter 1 (GLUT1) expression correlated to the SUV_mean. Vascularity (CD34 expression) and tumour hypoxia (carbonic anhydrase IX expression) did not correlate with ¹⁸F-FDG PET parameters.

Conclusion

In conclusion, repeatability of SUV_mean and SUV_max was mainly affected by preceding systemic therapy. The repeatability of tumour volume and TLG could be improved using more advanced and robust delineation approaches such as FLAB, which is recommended when ¹⁸F-FDG PET is utilized for volume or TLG measurements. Improvement of repeatability of PET measurements, for instance by dynamic PET scanning protocols, is probably necessary to effectively use PET for early response monitoring.     

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.     

The impact of systemic chemotherapy on testicular FDG activity in young men with Hodgkin’s lymphoma

Purpose

Based on prior reports suggesting a positive correlation between fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT and total sperm count and concentration, we sought to identify changes in testicular FDG uptake over the course of chemotherapy in young men with Hodgkin’s lymphoma.

Methods

Fifty-two patients with a mean age of 24.2 years (range 15.5–44.4) at diagnosis monitored with FDG PET/CT to assess treatment response for Hodgkin’s lymphoma were selected for this retrospective analysis under an Institutional Review Board waiver. Of the patients, 26 were treated with a chemotherapy regimen known to cause prolonged and sometimes permanent azoospermia (BEACOPP—bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) and 26 with a regimen known to have a much milder effect on gonadal function (ABVD—doxorubicin, bleomycin, vincristine, and dacarbazine). Each patient underwent one FDG PET/CT before treatment and at least one FDG PET/CT after start of chemotherapy. In all examinations, FDG activity was measured in the testes with different quantification metrics: maximum standardized uptake value (SUV_max), SUV_mean, functional volume (FV) and total testicular glycolysis (TTG), and blood pool activity determined (SUV_mean).

Results

Testicular FDG uptake (SUV_max) was significantly associated with blood pool activity (p?<?0.001). Furthermore, testicular FDG uptake metrics incorporating volume (e.g., FV and TTG) were associated with age. There was no significant change in SUV_max, SUV_mean, FV, and TTG from the PET/CT at baseline to the PET/CTs over the course of chemotherapy either for patients treated with BEACOPP or for patients treated with ABVD.

Conclusion

For patients undergoing chemotherapy for Hodgkin’s lymphoma, there is a significant association between testicular FDG uptake and blood pool activity, but no significant changes in FDG uptake over the course of chemotherapy. Therefore, FDG uptake may not be a feasible surrogate marker for fertility monitoring in patients with Hodgkin’s lymphoma undergoing chemotherapy.     

Glucose corrected standardized uptake value (SUVgluc) in the evaluation of brain lesions with 18F-FDG PET

Purpose

To retrospectively assess the utility of ¹⁸F fluorodeoxyglucose (FDG) positron emission tomography (PET) images of standardized uptake values corrected for blood glucose (SUV_gluc), and to compare this to various quantitative methods to identify the presence or absence of high grade malignancy.

Methods

A retrospective review in 42 patients, found 81 central nervous system (CNS) lesions. Fifty one were malignant and 30 were benign or post treatment changes based on pathology (n?=?32) and on clinical outcome (n?=?49). Dynamic FDG PET scans were processed to generate parametric images of SUV_gluc, SUV, glucose metabolic rate (GMR), and lesion to cerebellum ratios (SUV_Rc), and contralateral white matter ratios (SUV_Rw). The SUV_gluc was calculated from $ {{{\mathrm{SU}{{\mathrm{V}}_{\max }}*\mathrm{BG}}} \left/ {{\left[ {100\,\mathrm{mg}/\mathrm{dl}} \right]}} \right.} $ , where SUV_max is the maximum SUV and BG is the blood glucose level (mg/dL).

Results

Using a malignant threshold for SUV_gluc of 4.5 and GMR of 13.0 μmole/min/100 g, the accuracies were similar for the SUV_gluc (80 %) and GMR (81 %) and were higher than the conventional SUV_max (73 %). The area under the receiver operating characteristic (ROC) curve for the SUV_gluc (0.8661) was better than that for the SUV_max (0.7955) (p?<?0.02) and was similar to those of the GMR (0.8694), SUV_Rc (0.8278), and SUV_Rw (0.8559).

Conclusion

These results suggest that the SUV_gluc may assist in the interpretation of FDG PET brain images in patients with CNS lesions. The SUV_gluc method avoids the complexity of kinetic modeling and the definition of a reference region.     

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.     

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.     

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.     

Arterial and fat tissue inflammation are highly correlated : a prospective 18F-FDG PET/CT study

Purpose

There is evidence that the link between obesity and cardiovascular disease might relate to inflammation in both fat tissue and the arterial wall. ¹⁸F-FDG uptake on PET is a surrogate marker of vessel wall inflammation. The aim of the study was to measure FDG uptake in both regions using PET and identify links between adipose and arterial inflammation.

Methods

Included in the study were 173 cardiovascular patients who were prospectively imaged with FDG PET/CT. Arterial FDG uptake was measured in the carotid arteries and ascending aorta. The same was done in fat tissue in the neck, the presternal region (both subcutaneous) and the pericardium. FDG uptake was quantified as average maximal target-to-background ratio (_meanTBR_max). Multivariate regression analyses were performed to identify significant associations between arterial and adipose tissue FDG uptake and clinical variables as given by the standardized correlation coefficient (β).

Results

FDG uptake values in all fat tissue regions were highly predictive of vascular FDG uptake in both the carotids (β 0.262, p?<?0.0001, in the neck subcutaneous region) and aorta (β 0.22, p?=?0.008, in the chest pericardial region; β 0.193, p?=?0.019, in the chest subcutaneous region). Obesity was significantly associated with elevated FDG uptake in adipose tissue (β 0.470, p?<?0.0001, in the neck subcutaneous region; β 0.619, p?=?0.028, in the chest subcutaneous region; β 0.978, p?=?0.035, in the chest pericardial region).

Conclusion

FDG uptake in diverse fat tissue regions was significantly associated with arterial FDG uptake, a reasonable surrogate of inflammation. Increasing body weight significantly predicted the level of fatty inflammation. FDG PET therefore provides imaging evidence of an inflammatory link between fat tissue and the vasculature in patients with cardiovascular disease.     

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.     

Assessment of aortitis by semiquantitative analysis of 180-min 18F-FDG PET/CT acquisition images

Purpose

The aim of this study was to evaluate the contribution of semiquantitative analysis of 180-min ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images for the assessment of aortitis in cases of suspected large vessel vasculitis (LVV) and to establish a threshold index for application in the clinical setting.

Methods

This prospective study included 43 patients (mean age 67.5?±?12.9?years) with suspicion of LVV (25 with a final diagnosis of aortitis). ¹⁸F-FDG PET/CT scan was acquired 180 min after injection of 7 MBq/kg of ¹⁸F-FDG. A semiquantitative analysis was performed calculating the aortic wall maximum standardized uptake value (SUV_max) (T), the lumen SUV_max (B) and the target to background ratio (TBR). These results were also compared with those obtained in a control population.

Results

The mean aortic wall SUV_max was 2.00?±?0.62 for patients with aortitis and 1.45?±?0.31 for patients without aortitis (p?p?max (0.997 vs 0.871). The highest sensitivity and specificity was obtained for a TBR of 1.34 (sensitivity 100 %, specificity 94.4 %).

Conclusion

Semiquantitative analysis of PET/CT images acquired 180 min after ¹⁸F-FDG injection and the TBR index of 1.34 show very high accuracy and, therefore, are strongly recommended for the diagnosis of aortitis in the clinical setting.     

Predictive value of early and late residual 18F-fluorodeoxyglucose and 18F-fluorothymidine uptake using different SUV measurements in patients with non-small-cell lung cancer treated with erlotinib

Purpose

To evaluate the predictive value of early and late residual ¹⁸F-fluorodeoxyglucose (FDG) and ¹⁸F-fluorothymidine (FLT) uptake using different SUV measurements in PET in patients with advanced non-small-cell lung cancer (NSCLC) treated with erlotinib.

Methods

We retrospectively reviewed data from 30 patients with untreated stage IV NSCLC who had undergone a combined FDG PET and FLT PET scan at 1?week (early) and 6?weeks (late) after the start of erlotinib treatment. Early and late residual FDG and FLT uptake were measured in up to five lesions per scan with different quantitative standardized uptake values (SUV_max, SUV_2Dpeak, SUV_3Dpeak, SUV₅₀, SUV_A50, SUV_A41) and compared with short-term outcome (progression vs. nonprogression after 6?weeks of erlotinib treatment). Receiver-operating characteristics (ROC) curve analysis was used to determine the optimal cut-off value for detecting nonprogression after 6?weeks. Kaplan-Meier analysis and the log-rank test were used to evaluate the association between residual uptake and progression-free survival (PFS).

Results

Nonprogression after 6?weeks was associated with a significantly lower early and late residual FDG uptake, measured with different quantitative parameters. In contrast, nonprogression after 6?weeks was not associated with early and late residual FLT uptake. Furthermore, patients with a lower early residual FDG uptake measured in terms of SUV_max and SUV_2Dpeak had a significantly prolonged PFS (282?days vs. 118?days; p?=?0.022) than patients with higher values. Similarly, lower late residual FDG uptake and early residual FLT uptake measured in terms of SUV_3Dpeak, SUV_A50 and SUV_A41, and late FLT uptake measured in terms of SUV_3Dpeak and SUV_A50 was associated with an improved PFS.

Conclusion

Early and late residual FDG uptake, measured using different quantitative SUV parameters, are predictive factors for short-term outcome in patients with advanced NSCLC treated with erlotinib. Additionally, low residual FDG and FLT uptake early and late in the course of erlotinib treatment is associated with improved PFS.     

The value of 18F-FDG PET/CT in the management of malignant peripheral nerve sheath tumors

Purpose

Our objective was to determine how positron emission tomography (PET)/CT had been used in the clinical treatment of malignant peripheral nerve sheath tumor (MPNST) patients at The University of Texas MD Anderson Cancer Center.

Methods

We reviewed a database of MPNST patients referred to MD Anderson Cancer Center during 1995–2011. We enrolled 47 patients who underwent PET/CT imaging. Disease stage was based on conventional imaging and PET/CT findings using National Comprehensive Cancer Network (NCCN) guidelines. Treatment strategies based on PET/CT and conventional imaging were determined by chart review. The maximum and mean standardized uptake values (SUV_max, SUV_mean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), change in SUV_max, change in MTV, and change in TLG were calculated from the PET/CT studies before and after treatment. Response prediction was based on imaging studies performed before and after therapy and categorized as positive or negative for residual tumor. Clinical outcome was determined from chart review.

Results

PET/CT was performed for staging in 16 patients, for restaging in 29 patients, and for surveillance in 2 patients. Of the patients, 88 % were correctly staged with PET/CT, whereas 75 % were correctly staged with conventional imaging. The sensitivity to detect local recurrence and distant metastasis at restaging was 100 and 100 % for PET/CT compared to 86 and 83 % for conventional imaging, respectively. PET/CT findings resulted in treatment changes in 31 % (5/16) and 14 % (4/29) of patients at staging and restaging, respectively. Recurrence, MTV, and TLG were prognostic factors for survival, whereas SUV_max and SUV_mean were not predictive. For 21 patients who had imaging studies performed both before and after treatment, PET/CT was better at predicting outcome (overall survival, progression-free survival) than conventional imaging. A decreasing SUV_max ≥ 30 % and decrease in TLG and MTV were significant predictors for overall and progression-free survival.

Conclusion

PET/CT is valuable in MPNST management because of its high accuracy in staging and high sensitivity and accuracy in restaging as well as improvements in treatment planning. MTV from baseline staging studies is predictive of survival. Additionally, change in SUV_max, TLG, and MTV accurately predicted outcomes after treatment.     

Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer

Purpose

The aim of this study was to determine the impact of the main clinicopathological and biological prognostic factors of breast cancer on ¹⁸F-fluorodeoxyglucose (FDG) uptake. Only women with tumours larger than 20?mm (T2?CT4) were included in order to minimize bias of partial volume effect.

Methods

In this prospective study, 132 consecutive women received FDG PET/CT imaging before starting neoadjuvant chemotherapy. Maximum standardized uptake values (SUV_max) were compared to tumour characteristics as assessed on core biopsy.

Results

There was no influence of T and N stage on SUV. Invasive ductal carcinoma showed higher SUV than lobular carcinoma. However, the highest uptake was found for metaplastic tumours, representing 5% of patients in this series. Several biological features usually considered as bad prognostic factors were associated with an increase in FDG uptake: the median of SUV_max was 9.7 for grade 3 tumours vs 4.8 for the lower grades (p?p?=?0.003); triple-negative tumours (oestrogen and progesterone receptor negative, no overexpression of c-erbB-2) had an SUV of 9.2 vs 5.8 for all others (p = 0005); p53 mutated tumours also had significantly higher SUV (7.8 vs 5.0; p?Conclusion Knowledge of the factors influencing uptake is important when interpreting FDG PET/CT scans. Also, findings that FDG uptake is highest in those patients with poor prognostic features (high grade, hormone receptor negativity, triple negativity, metaplastic tumours) is helpful to determine who are the best candidates for baseline staging.     

Prediction of central lymph node metastasis from papillary thyroid microcarcinoma by 18F-fluorodeoxyglucose PET/CT and ultrasonography

Purpose

The presence of central lymph node (LN) metastasis increases the risk of cervical LN recurrence or distant metastasis in patients with papillary thyroid microcarcinoma (PTMC). We investigated the value of preoperative ¹⁸F-fluoro-2-deoxy-d-glucose-positron emission tomography (FDG PET)?Ccomputerized tomography (CT) and ultrasonography (US) to predict central LN metastasis from PTMC.

Patients and methods

Two hundred patients with newly diagnosed unifocal PTMC were enrolled. Preoperative FDG PET?CCT was performed, and the highest SUV (SUV_max) of focally increased uptake at thyroid was measured. Tumor size was measured using preoperative US. Uni- and multivariate analyses were performed using the presence of focally increased uptake at thyroid (FDG positivity), SUV_max, tumor size, and clinical risk factor for central LN metastasis. ROC curves for risk factors were then analyzed. These analyses were undertaken in two groups: the all patients group and the FDG-positive group. Finally, we combined risk factors associated with central LN metastasis to improve predictive accuracy.

Results

Tumor size >6?mm was associated with central LN metastasis. FDG positivity was identified in 110 patients (55.0?%) and the SUV_max ranged from 1.8 to 12.8 (median 3.0). In FDG-positive group, SUV_max >2.8 was associated with central LN metastasis. Addition of SUV_max >2.8 to size >6?mm of PTMC improved sensitivity of predicting central LN metastasis from 55.0 to 67.5?%, while specificity remained at 70.6?%.

Conclusion

Both FDG PET?CCT and US are valuable for preoperative prediction of central LN metastasis from PTMC. Combined use of SUV_max and tumor size improves sensitivity without changing specificity.     

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.     

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.     

Correlation between [18F]FDG PET/CT and volume perfusion CT in primary tumours and mediastinal lymph nodes of non-small-cell lung cancer

Purpose

The aim of this study was to investigate correlations between glucose metabolism as determined by [¹⁸F]FDG PET/CT and tumour perfusion as quantified by volume perfusion CT in primary tumours and mediastinal lymph nodes (MLN) of patients with non-small-cell lung cancer (NSCLC).

Methods

Enrolled in the study were 17 patients with NSCLC. [¹⁸F]FDG uptake was quantified in terms of SUV_max and SUV_avg. Blood flow (BF), blood volume (BV) and flow extraction product (K^trans) were determined as perfusion parameters. The correlations between the perfusion parameters and [¹⁸F]FDG uptake values were subsequently evaluated.

Results

For the primary tumours, no correlations were found between perfusion parameters and [¹⁸F]FDG uptake. In MLN, there were negative correlations between BF and SUV_avg (r?=??0.383), BV and SUV_avg (r?=??0.406), and BV and SUV_max (r?=??0.377), but not between BF and SUV_max, K^trans and SUV_avg, or K^trans and SUV_max. Additionally, in MLN with SUV_max >2.5 there were negative correlations between BF and SUV_avg (r?=??0.510), BV and SUV_avg (r?=??0.390), BF and SUV_max (r?=??0.536), as well as BV and SUV_max (r?=??0.346).

Conclusion

Perfusion and glucose metabolism seemed to be uncoupled in large primary tumours, but an inverse correlation was observed in MLN. This information may help improve therapy planning and response evaluation.     

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.