Correlation of HIF-1α/HIF-2α expression with FDG uptake in lung adenocarcinoma

Objectives

Hypoxia is a key element involved in the development and progression of tumors. HIF-1α may transiently induce and mediate the response to acute and severe hypoxia, while HIF-2α may induce a longer response and may control the response to chronic and moderate hypoxia. Hypoxia increases the cellular uptake of FDG. Therefore, HIF may play an important role in the process of the cellular uptake of FDG. The aim of this study was to compare HIF-1α/HIF-2α expression with FDG uptake, Glut-1 expression, and prognosis in the patients with lung adenocarcinoma and to investigate the role of HIF-1α/HIF-2α in the uptake of FDG in lung adenocarcinoma.

Methods

In the current work, we compared the immunohistochemical expression of HIF-1α and HIF-2α in surgical specimens of 44 patients with lung adenocarcinoma. The relationships between HIF-α expression and Glut-1 expression, FDG uptake, and clinicopathological factors, including prognosis, were analyzed.

Results

There was a marginal association between HIF-1α and HIF-2α expressions (P = 0.076). We found a significant correlation between HIF-2α expression and FDG uptake (P = 0.0001). HIF-1α expression showed a marginal association with FDG uptake (P = 0.066). FDG uptake correlated more significantly with HIF-2α expression than with HIF-1α expression. A significant correlation was noticed between Glut-1 expression and both HIF-1α and HIF-2α expressions (P = 0.005 and P = 0.003, respectively). Univariate analysis of disease-free survival demonstrated that FDG uptake and HIF-2α expression, but not HIF-1α expression, were related to recurrence (P < 0.0001).

Conclusion

FDG uptake correlated more significantly with HIF-2α expression than with HIF-1α expression, and both FDG uptake and HIF-2α expression, but not HIF-1α expression was correlated with post-operative recurrence in the patients with lung adenocarcinoma. These results suggest that both FDG uptake and HIF-2α expression may represent a more aggressive phenotype and that HIF-2α may play a more important role than HIF-1α in the uptake of FDG in lung adenocarcinoma.

     

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.

     

Prognostic value of metabolic indices and bone marrow uptake pattern on preoperative 18F–FDG PET/CT in pediatric patients with neuroblastoma

Purpose

To evaluate the prognostic value of metabolic parameters and bone marrow uptake (BMU) patterns on pretherapeutic 18-F-fluorodeoxyglucose (18F–FDG) positron emission tomography/computed tomography (PET/CT) in pediatric patients with neuroblastoma (NB).

Patients and methods

Forty-seven pediatric patients with newly diagnosed neuroblastoma who underwent 18F–FDG PET/CT were retrospectively reviewed. Clinicopathological factors and metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and bone marrow uptake patterns on PET/CT were compared to predict recurrence-free survival (RFS) and overall survival (OS) by univariate and multivariate analysis.

Results

During the follow-up period, 27 (57.4%) patients experienced recurrence. MTV (P = 0.001), TLG (P = 0.004) and BMU patterns (P = 0.025) remained significant predictive factors for tumor recurrence, along with tumor size, histology, stage, lactate dehydrogenase (LDH) and other distant metastasis (except bone metastasis). Univariate analysis showed that histology, stage, tumor size (>37.25 cm), other distant metastasis, MTV (>88.10cm³) and TLG (>1045.2 g) and BMU patterns correlated with both RFS and OS (P < 0.05). On multivariate analysis, TLG remained the only independent prognostic factor for RFS (P = 0.016) and OS (P = 0.012), and BMU patterns and MTV were statistically significant for OS (P = 0.024 and P = 0.038, respectively).

Conclusion

Pretherapeutic 18F-FDG PET/CT can provide reliable prognostic information for neuroblastoma pediatric patients, and patients with high MTV, TLG and focal bone marrow (unifocal and multifocal) uptake on PET/CT may have inferior outcomes during subsequent treatment.

     

Metformin discontinuation less than 72 h is suboptimal for F-18 FDG PET/CT interpretation of the bowel

Objective

Metformin-induced [F-18] fluorodeoxyglucose (FDG) bowel uptake can hinder positron emission tomography/computed tomography (PET/CT) evaluation of the bowel. This study aimed to investigate the segmental bowel uptake of FDG according to metformin discontinuation times up to 72 h.

Methods

We retrospectively divided 240 diabetic patients into four groups: metformin discontinuation <24 h (group A; n = 86), 24–48 h (group B; n = 40), 48–72 h (group C; n = 12), and no metformin (control group; n = 102). Segmental FDG bowel uptakes were measured visually (four-point scale) and semi-quantitatively (maximum standardized uptake value).

Results

Compared with the control group, FDG uptake increased significantly from the ileum to the rectosigmoid colon in group A, from the transverse to the rectosigmoid colon in group B, and from the descending colon to the rectosigmoid colon in group C in both visual and semi-quantitative analyses.

Conclusions

Metformin discontinuation for <72 h is likely suboptimal for PET/CT image interpretation, especially with respect to the distal segments of the colon.

     

Increased FDG uptake on late-treatment PET in non-tumour-affected oesophagus is prognostic for pathological complete response and disease recurrence in patients undergoing neoadjuvant radiochemotherapy

Purpose

Early side effects including oesophagitis are potential prognostic factors in patients undergoing radiochemotherapy (RCT) for locally advanced oesophageal cancer (LAEC). We assessed the prognostic value of ¹⁸F-fluorodeoxyglucose (FDG) uptake within irradiated non-tumour-affected oesophagus (NTO) during restaging positron emission tomography (PET) as a surrogate for inflammation/oesophagitis.

Methods

This retrospective evaluation included 64 patients with LAEC who had completed neoadjuvant RCT and had successful oncological resection. All patients underwent FDG PET/CT before and after RCT. In the restaging PET scan maximum and mean standardized uptake values (SUV_max, SUV_mean) were determined in the tumour and NTO. Univariate Cox regression with respect to overall survival, local control, distant metastases and treatment failure was performed. Independence of clinically relevant parameters was tested in a multivariate Cox regression analysis.

Results

Increased FDG uptake, measured in terms of SUV_mean in NTO during restaging was significantly associated with complete pathological remission (p = 0.002) and did not show a high correlation with FDG response of the tumour (rho < 0.3). In the univariate analysis, increased SUV_max and SUV_mean in NTO was associated with improved overall survival (p = 0.011, p = 0.004), better local control (p = 0.051, p = 0.044), a lower rate of treatment failure (p < 0.001 for both) and development of distant metastases (p = 0.012, p = 0.001). In the multivariate analysis, SUV_max and SUV_mean in NTO remained a significant prognostic factor for treatment failure (p < 0.001, p = 0.004) and distant metastases (p = 0.040, p = 0.011).

Conclusions

FDG uptake in irradiated normal tissues measured on restaging PET has significant prognostic value in patients undergoing neoadjuvant RCT for LAEC. This effect may potentially be of use in treatment personalization.

     

Whole body MRI with qualitative and quantitative analysis of DWI for assessment of bone marrow involvement in lymphoma

Aim

Our study aimed to investigate the role of qualitative and quantitative whole body MRI with DWI for assessment of bone marrow involvement (BMI) in newly diagnosed lymphoma using FDG PET–CT and bone marrow biopsy (BMB) as reference standard.

Materials and methods

We retrospectively evaluated 56 patients with newly diagnosed lymphoma (21 Hodgkin’s lymphoma and 35 non-Hodgkin’s lymphoma) who underwent random unilateral BMB, FDG PET–CT and Wb-MRI-DWI for initial staging. In a patient-based analysis, results of Wb-MRI-DWI were compared with FDG PET–CT and BMB. For quantitative analysis, mean ADC values of posterior iliac crest were correlated with BMI and bone marrow cellularity.

Results

WB-MR-DWI obtained excellent concordance with FDG PET–CT both in HL (k = 1.000; 95% CI 1.000–1.000) and in DLBCL (k = 1.000; 95% CI 1.000–1.000). In other NHL, WB-MRI-DWI obtained a good correlation with BMB (k = 0.611; 95% CI 0.295–0.927) while FDG PET–CT had poor concordance (k = 0.067; 95% CI 0.372–0.505). WB-MR-DWI has no false negative errors but 4 false positive results consisting in focal lesions consensually reported by FDG PET–CT and resolved after therapy. No significant correlation between ADC mean value and BMI was found (p = 0.0586).

Conclusion

Our data suggest that Wb-MRI-DWI is a valid technique for BMI assessment in lymphoma patients, thanks to its excellent concordance with FDG PET–CT and good concordance with BMB (superior than FDG PET–CT). If further investigations will confirm our results on larger patient groups, it could become a useful tool in the clinical workup.

     

Malignancy rate of biopsied suspicious bone lesions identified on FDG PET/CT

Purpose

To determine the malignancy rate of bone lesions identified on FDG PET/CT in patients who have undergone CT-guided biopsy because of the suspicion of malignancy.

Methods

This single-centre retrospective study spanned eight consecutive years and included all patients who underwent both FDG PET/CT and CT-guided bone biopsy because of the suspicion of malignancy. The positive predictive value (PPV) for malignancy was calculated, and different patient and imaging characteristics were compared between malignant and benign bone lesions.

Results

Of 102 included patients with bone lesions that all showed FDG uptake exceeding mediastinal uptake, bone biopsy showed a malignant lesion in 91 patients, yielding a PPV for malignancy of 89.2 % (95 % CI 81.7 – 93.9 %). In the 94 patients with bone lesions that showed FDG uptake exceeding liver uptake, bone biopsy showed a malignant lesion in 83 patients, yielding a PPV for malignancy of 88.3 % (95 % CI 80.1 – 93.5 %). Higher age, bone marrow replacement of the lesion seen on CT, expansion of the lesion seen on CT, and presence of multifocal lesions on FDG PET/CT were significantly more frequent in patients with malignant lesions than in those with benign bone lesions (P?=?0.044, P?=?0.009, P?=?0.015, and P?=?0.019, respectively). Furthermore, there was a trend towards a higher incidence of cortical destruction (P?=?0.056) and surrounding soft tissue mass (P?=?0.063) in patients with malignant bone lesions.

Conclusion

The PPV for malignancy of suspicious bone lesions identified on FDG PET/CT is not sufficiently high to justify changes in patient management without histopathological confirmation. Nevertheless, ancillary patient and imaging characteristics may increase the likelihood of a malignant bone lesion.

     

Prognostic value of lymph node-to-primary tumor standardized uptake value ratio in endometrioid endometrial carcinoma

Purpose

To determine whether the relative metabolic activity of pelvic or para-aortic LN compared with that of primary tumor measured by preoperative [¹⁸F]FDG PET/CT scan has prognostic value in patients with endometrioid endometrial carcinoma.

Methods

We retrospectively reviewed patients with endometrioid endometrial carcinoma who underwent preoperative [¹⁸F]FDG PET/CT scans. Prognostic values of PET/CT-derived metabolic variables such as maximum standardized uptake value (SUV) of the primary endometrial carcinoma (SUV_Tumor) and LN (SUV_LN), and the LN-to-endometrial carcinoma SUV ratio (SUV_LN / SUV_Tumor) were assessed.

Results

Clinico-pathological data, imaging data, and treatment results were reviewed for 107 eligible patients. Median post-surgical follow-up was 23 months (range, 6–60), and 7 (6.5%) patients experienced recurrence. Regression analysis showed that SUV_LN / SUV_Tumor (P < 0.001), SUV_LN (P = 0.003), International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.006), and tumor grade (P = 0.011) were risk factors of recurrence. Multivariate regression analysis revealed that FIGO stage (P = 0.034) was the independent risk factor of recurrence. SUV_LN / SUV_Tumor showed significant correlation with FIGO stage (P < 0.001), LN metastasis (P < 0.001), lymphovascular space invasion (P < 0.001), recurrence (P = 0.001), tumor grade (P < 0.001), and deep myometrial invasion of tumor (P = 0.022). Patient groups categorized by SUV_LN / SUV_Tumor showed significant difference in progression-free survival (Log-rank test, P = 0.001).

Conclusions

Preoperative SUV_LN / SUV_Tumor measured by [¹⁸F]FDG PET/CT was significantly associated with recurrence, and may become a novel prognostic factor in patients with endometrioid endometrial carcinoma.

     

Heterogeneity index evaluated by slope of linear regression on <Superscript>18</Superscript>F-FDG PET/CT as a prognostic marker for predicting tumor recurrence in pancreatic ductal adenocarcinoma

Purpose

¹⁸F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been investigated as a method to predict pancreatic cancer recurrence after pancreatic surgery. We evaluated the recently introduced heterogeneity indices of ¹⁸F-FDG PET/CT used for predicting pancreatic cancer recurrence after surgery and compared them with current clinicopathologic and ¹⁸F-FDG PET/CT parameters.

Methods

A total of 93 pancreatic ductal adenocarcinoma patients (M:F = 60:33, mean age = 64.2 ± 9.1 years) who underwent preoperative ¹⁸F-FDG PET/CT following pancreatic surgery were retrospectively enrolled. The standardized uptake values (SUVs) and tumor-to-background ratios (TBR) were measured on each ¹⁸F-FDG PET/CT, as metabolic parameters. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were examined as volumetric parameters. The coefficient of variance (heterogeneity index-1; SUVmean divided by the standard deviation) and linear regression slopes (heterogeneity index-2) of the MTV, according to SUV thresholds of 2.0, 2.5 and 3.0, were evaluated as heterogeneity indices. Predictive values of clinicopathologic and ¹⁸F-FDG PET/CT parameters and heterogeneity indices were compared in terms of pancreatic cancer recurrence.

Results

Seventy patients (75.3%) showed recurrence after pancreatic cancer surgery (mean recurrence = 9.4 ± 8.4 months). Comparing the recurrence and no recurrence patients, all of the ¹⁸F-FDG PET/CT parameters and heterogeneity indices demonstrated significant differences. In univariate Cox-regression analyses, MTV (P = 0.013), TLG (P = 0.007), and heterogeneity index-2 (P = 0.027) were significant. Among the clinicopathologic parameters, CA19–9 (P = 0.025) and venous invasion (P = 0.002) were selected as significant parameters. In multivariate Cox-regression analyses, MTV (P = 0.005), TLG (P = 0.004), and heterogeneity index-2 (P = 0.016) with venous invasion (P < 0.001, 0.001, and 0.001, respectively) demonstrated significant results.

Conclusions

The heterogeneity index obtained using the linear regression slope, could be an effective predictor of pancreatic cancer recurrence after pancreatic cancer surgery, in addition to ¹⁸F-FDG PET/CT volumetric parameters and clinicopathologic parameters.

     

<Superscript>18</Superscript>F–fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment

Purpose

Sorafenib, an oral multikinase inhibitor, is a recommended treatment option available for patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). This study aimed to evaluate the performance of ¹⁸F–fluorodeoxyglucose positron emission tomography (¹⁸F–FDG PET) for predicting tumour progression during sorafenib treatment.

Methods

We formed a retrospective cohort comprising patients treated with sorafenib for at least 30 days and undergoing ¹⁸F–FDG PET/CT within 1 month before treatment. For statistical analyses, the tumour-to-liver standardised uptake value (SUV) ratio (TLR) of the most hypermetabolic lesion was measured.

Results

Among a total of 35 patients, two obtained partial remission, and 11 showed stable disease after the first response evaluation. Patients with a TLR ≥ 2.9 (n = 17) had a median overall survival (OS) of 3.7 months after sorafenib treatment, whereas patients with a TLR < 2.9 (n = 18) had median OS of 12.2 months (P < 0.001), although the disease control rate was not significantly different between the two groups. Pretreatment TLR ≥ 2.9 (hazard ratio [HR] = 6.318, P = 0.002) and Child-Pugh class B (HR = 4.316, P = 0.044) were poor prognostic factors for OS, and a TLR ≥ 2.9 (HR = 2.911, P = 0.024) was the only poor prognostic factor for progression-free survival in a multivariate analysis.

Conclusion

Pretreatment tumour metabolic activity assessed by ¹⁸F–FDG PET is an independent prognostic factor for survival in patients with BCLC-C stage HCC receiving sorafenib monotherapy, although it may not predict tumour response to the treatment.

     

The Predictive Values of Lesion Size,F-18 FDG Avidity and I-131 Avidity for the Clinical Outcome of I-131 Treatment in Patients with Metastatic Differentiated Thyroid Carcinoma Only in the Lung

Purpose

We aimed to evaluate the prognostic values of radiography, F-18 FDG PET, and I-131 whole body scans in patients with lung-only metastasis from differentiated thyroid carcinoma (DTC).

Methods

Between 1998 and 2013, we included 31 patients (F: 26, M: 5) with lung-only metastasis from DTC who had been treated with I-131 and underwent PET. Lung metastasis was categorized according to the size (macronodular ≥1.0 cm vs. micronodular <1.0 cm), FDG avidity (avid vs. non-avid), and I-131 avidity (avid vs. non-avid). Progression-free survival (PFS) was evaluated for each patient.

Results

Among 31 patients, seven (23%) had macronodular lung metastasis, 26 (84%) had FDG avid lung metastasis, and 16 (52%) had I-131 avid lung metastasis. During the median follow-up period of 9.4 y, median PFS was 6.1 y. Based on Kaplan-Meier analysis, macronodular lung metastasis (p = 0.017) and I-131 non-avid lung metastasis (p = 0.059) were significantly associated with worse outcomes, but FDG avid lung metastasis was not (p = 0.135). Patients with FDG non-avid lung metastasis did not experience disease progression during follow-up, while 11 of 26 patients (42%) experienced disease progression. Based on univariate analysis, the hazard ratio for a poor prognosis was 3.78 (p = 0.029) for macronodular lung metastasis and 3.29 (p = 0.079) for I-131 non-avid lung metastasis.

Conclusions

Macronodular and I-131 non-avid lung metastasis were associated with a poor prognosis in lung-only metastasis from DTC. Although FDG avid lung metastasis may be associated with a poor prognosis, a larger-scale study is needed.

     

Strong association of epidermal growth factor receptor status with breast cancer FDG uptake

Purpose

Imaging tumor FDG uptake could complement breast cancer biomarkers of risk and treatment response. Although breast cancer FDG uptake is reputedly influenced by major biomarker states, the role of epidermal growth factor receptor (EGFR) expression remains largely unexplored.

Methods

This is a retrospective study that included 499 patients with primary breast cancer at initial presentation. Tumor FDG uptake was measured on pretreatment PET/CT as maximum standardized uptake value (SUVmax), and biomarkers were assessed by immunohistochemistry of tumor tissue. Regression analysis was performed for predictors of high tumor FDG uptake (SUVmax ≥ 8.6).

Results

SUVmax was higher in ER- (36.5%; 11.2 ± 6.0 vs. 8.3 ± 5.3), PR- (42.3%; 10.9 ± 6.0 vs. 8.2 ± 5.2), and triple-negative tumors (19.8%; 12.0 ± 6.9 vs. 8.7 ± 5.2; all p < 0.0001). EGFR expression (28.5%) was more frequent in ER-, PR-, triple-negative, cytokeratin 5/6 (CK5/6) + and mutant P53 (mP53) + tumors (all p < 0.0001). EGFR+ was associated with higher SUVmax among all tumors (11.9 ± 6.0 vs. 8.3 ± 5.3), ER- tumors (p < 0.0001), PR- and + tumors (p < 0.0001 and 0.027), hormone receptor- and + tumors (p < 0.0001 and 0.004), human epidermal growth factor receptor 2 (HER2)- and + tumors (p < 0.0001 and 0.006), non-triple negative tumors (p < 0.0001), CK5/6- and + tumors (p = 0.021 and <0.0001), and mP53- and + tumors (p < 0.0001 and 0.008). Tumors had high FDG uptake in 73.2% of EGFR+ and 40.6% of EGFR- tumors. On regression analysis, significant multivariate predictors of high tumor FDG uptake were large size, EGFR+ and CK5/6+ for the entire subjects, and EGFR+ and CK5/6+ for ER- and hormone receptor negative subgroups. High FDG uptake was able to sub-stratify EGFR+ tumors that were more likely to be ER- and CK5/6+, and EGFR- tumors more likely to be mP53 +.

Conclusions

Primary breast tumor FDG uptake is strongly influenced by EGFR status beyond that by other major biomarkers including hormone receptor and HER2 status, and EGFR expression is a strong independent predictor of high breast tumor FDG uptake.

     

<Superscript>11</Superscript>C-methylaminoisobutyric acid (MeAIB) PET for evaluation of prostate cancer: compared with <Superscript>18</Superscript>F-fluorodeoxyglucose PET

Objective

α-N-methyl-¹¹C-methylaminoisobutyric acid (¹¹C-MeAIB) is a selective substrate of system A amino acid transport, and known to accumulate in malignant lesions. The aim of this study was to evaluate the utility of MeAIB PET for the assessment of prostate cancer, compared with FDG PET.

Methods

Thirty-four men (age range 57–77 years) with prostate cancer were prospectively enrolled, and underwent MeAIB PET and FDG PET between January 2011 and January 2013. MeAIB PET and FDG PET were performed at 20 and 50 min post-injection, respectively. SUVmax of the prostate was calculated, and visual analysis was conducted for MeAIB and FDG PET studies. MRI images were visually evaluated if available. All patients received total prostatectomy subsequently, and imaging findings were compared with pathological results, including T stage, Gleason score, and tumor size. The patient-based and lesion-based sensitivity and specificity were calculated according to pathological significant cancer.

Results

Mean value of SUVmax of ¹¹C-MeAIB PET and ¹⁸F-FDG PET in prostate cancer were 3.18 (±1.90, range; 1.55–9.57) and 3.88 (±2.85, range; 2.04–14.47). MeAIB PET and FDG PET were positive by visual analysis in 47.1 % (16/34) and 44.1 % (15/34) of the patients. MRI was positive in 51.5 % (17/33). Pathological stage and Gleason score were as follows: Stage 2 (n = 23), 3 (n = 8), and 4 (n = 3); Gleason score 6 (n = 13), 7 (n = 16), 8 (n = 3), and 9 (n = 2). The sensitivities tended to be higher according to higher pathological T stage or Gleason sum score for both MeAIB and FDG PET studies. Visual analysis of both MeAIB PET and FDG PET had significant correlation with extraprostatic extension (p < 0.05). MeAIB PET and FDG PET had complementary results by visual analysis in the assessment of prostate cancer. The patient-based sensitivity of MeAIB PET, FDG PET, and MRI were 51.6, 48.4, and 56.7 %, respectively. The patient-based specificity of these modalities was 100 % for each modality.

Conclusions

MeAIB PET has better diagnostic results than FDG PET for the assessment of significant prostate cancer, and these PET studies showed complementary results. MRI has even better diagnostic results than ¹¹C-MeAIB PET. MeAIB accumulates in prostate cancer, which indicates that the system A amino acid transport pathway is activated in prostate cancer.

     

The effects of 18-h fasting with low-carbohydrate diet preparation on suppressed physiological myocardial <Superscript>18</Superscript>F-fluorodeoxyglucose (FDG) uptake and possible minimal effects of unfractionated heparin use in patients with suspected cardiac involvement sarcoidosis

Background

¹⁸F-fluorodeoxyglucose (FDG) PET plays an important role in the detection of cardiac involvement sarcoidosis (CS). However, diffuse left ventricle (LV) wall uptake sometimes makes it difficult to distinguish between positive uptake and physiological uptake. The aims of this study were to evaluate the effects of 18-h fasting with low-carbohydrate diet (LCD) vs a minimum of 6-h fasting preparations on diffuse LV FDG uptake and free fatty acid (FFA) levels in patients with suspected CS.

Methods

Eighty-two patients with suspected CS were divided into 2 preparation protocols: one with a minimum 6-h fast without LCD preparation (group A, n = 58) and the other with a minimum 18-h fast with LCD preparation (group B, n = 24). All patients also received intravenous unfractionated heparin (UFH; 50 IU/kg) before the injection of FDG.

Results

Group A showed a higher percentage of diffuse LV uptake than did group B (27.6 vs 0.0%, P = .0041). Group B showed higher FFA levels (1159.1? ± ?393.0, 650.5? ± ?310.9 μEq/L, P < .0001) than did group A. Patients with diffuse LV uptake (n = 16) showed lower FFA levels than did other patients (n = 66) (432.1? ± ?296.1, 888.4? ± ?381.4 μEq/L, P < .0001). UFH administration significantly increased FFAs in both groups, even in the patients with diffuse LV FDG uptake.

Conclusions

The 18-h fast with LCD preparation significantly reduced diffuse LV uptake and increased FFA levels. In particular, the FFA level was significantly lower in patients with LV diffuse uptake than in patients without LV diffuse uptake. Acutely increasing plasma FFA through the use of UFH may not have a significant role in reducing physiological LV FDG uptake.

     

Prediction of breast cancer recurrence using lymph node metabolic and volumetric parameters from <Superscript>18</Superscript>F-FDG PET/CT in operable triple-negative breast cancer

Purpose

Triple-negative breast cancer has a poor prognosis. We evaluated several metabolic and volumetric parameters from preoperative ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the prognosis of triple-negative breast cancer and compared them with current clinicopathologic parameters.

Methods

A total of 228 patients with triple-negative breast cancer (mean age 47.0 ± 10.8 years, all women) who had undergone preoperative PET/CT were included. The PET/CT metabolic parameters evaluated included maximum, peak, and mean standardized uptake values (SUVmax, SUVpeak, and SUVmean, respectively). The volumetric parameters evaluated included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Metabolic and volumetric parameters were evaluated separately for tumor (T) and lymph nodes (N). The prognostic value of these parameters was compared with that of clinicopathologic parameters.

Results

All lymph node metabolic and volumetric parameters showed significant differences between patients with and without recurrence. However, tumor metabolic and volumetric parameters showed no significant differences. In a univariate survival analysis, all lymph node metabolic and volumetric parameters (SUVmax-N, SUVpeak-N, SUVmean-N, MTV-N, and TLG-N; all P < 0.001), T stage (P = 0.010), N stage (P < 0.001), and TNM stage (P < 0.001) were significant parameters. In a multivariate survival analysis, SUVmax-N (P = 0.005), MTV (P = 0.008), and TLG (P = 0.006) with TNM stage (all P < 0.001) were significant parameters.

Conclusions

Lymph node metabolic and volumetric parameters were significant predictors of recurrence in patients with triple-negative breast cancer after surgery. Lymph node metabolic and volumetric parameters were useful parameters for evaluating prognosis in patients with triple-negative breast cancer by ¹⁸F-FDG PET/CT, rather than tumor parameters.

     

Prognostic Value of Pre- and Post-Treatment FDG PET/CT Parameters in Small Cell Lung Cancer Patients

Purpose

To evaluate the prognostic value of PET parameters obtained from pre- and post-treatment FDG PET/CT examinations in patients with SCLC.

Methods

Fifty-nine patients with initially diagnosed SCLC from 2009 to 2014 were included and had chemotherapy and/or concurrent chemoradiotherapy. FDG PET/CT examinations were performed before (PET1) and after (PET2) treatment to evaluate treatment response. A region of interest was placed over the primary lesion and metastatic lymph nodes within the thoracic cavity. PET parameters including change from PET1 to PET2 (Δ in %) were acquired: SUVmax, SUVpeak, MTV2.5, TLG, ΔSUVmax, ΔSUVpeak, ΔMTV and ΔTLG. Patient characteristics including staging, age, sex, LDH and response evaluation by RECIST were surveyed. Statistical analysis was done using Kaplan-Meier method and Cox regression analysis with respect to OS and PFS.

Results

The median follow-up was 9.6 months (2.5–80.5 months). 27 patients were LD and 32 were ED. Forty-six patients (78.0%) had died, and median OS was 8.6 months; 51 patients (86%) showed disease progression, and median PFS was 2.5 months. On univariate analysis, patients with ED, high interval change (ΔSUVmax and ΔSUVpeak) and low PET2 parameters showed longer OS and PFS. Multivariate analyses demonstrated that ΔSUVpeak (HR 2.6, P = 0.002) was an independent prognostic factors for OS, and MTV2.5 of PET2 (HR 2.8, P = 0.001), disease stage (HR 2.7, P = 0.003) and RECIST (HR 2.0, P = 0.023) were independent prognostic factors for PFS.

Conclusions

Metabolic and volumetric PET parameters obtained from pre- and post-treatment FDG PET/CT examinations in patients with SCLC have significant prognostic information.

     

Evaluation of ECG-gated [<Superscript>11</Superscript>C]acetate PET for measuring left ventricular volumes,mass, and myocardial external efficiency

Background

Noninvasive estimation of myocardial external efficiency (MEE) requires measurements of left ventricular (LV) oxygen consumption with [¹¹C]acetate PET in addition to LV stroke volume and mass with cardiovascular magnetic resonance (CMR). Measuring LV geometry directly from ECG-gated [¹¹C]acetate PET might enable MEE evaluation from a single PET scan. Therefore, we sought to establish the accuracy of measuring LV volumes, mass, and MEE directly from ECG-gated [¹¹C]acetate PET.

Methods

Thirty-five subjects with aortic valve stenosis underwent ECG-gated [¹¹C]acetate PET and CMR. List mode PET data were rebinned into 16-bin ECG-gated uptake images before measuring LV volumes and mass using commercial software and compared to CMR. Dynamic datasets were used for calculation of mean LV oxygen consumption and MEE.

Results

LV mass, volumes, and ejection fraction measured by CMR and PET correlated strongly (r = 0.86-0.92, P < .001 for all), but were underestimated by PET (P < .001 for all except ESV P = .79). PET-based MEE, corrected for bias, correlated fairly with PET/CMR-based MEE (r = 0.60, P < .001, bias ?3 ± 21%, P = .56). PET-based MEE bias was strongly associated with LV wall thickness.

Conclusions

Although analysis-related improvements in accuracy are recommended, LV geometry estimated from ECG-gated [¹¹C]acetate PET correlate excellently with CMR and can indeed be used to evaluate MEE.

     

18F-FDG uptake in main arterial branches of patients with large vessel vasculitis: visual and semiquantitative analysis

Objective

Over the last decade, the contribution of ¹⁸F-FDG (FDG) PET/CT imaging to the diagnosis of large vessel vasculitis has been widely investigated. The aim of this study was to evaluate a more extensive role for PET/CT in grading vascular inflammation in patients with different clinical stages of disease.

Methods

The images of 66 PET/CT studies of 34 patients, performed at diagnosis and/or during follow-up were reviewed. FDG uptake in different regions of aorta and in its major branches was visually (regional Score: rS) and semiquantitatively (regional SUVmean: rSUV) assessed. The global vascular uptake was also evaluated for each study by summing all rSs (summed Score; sS) and averaging rSUVs (averaged SUV; aSUV). FDG uptake in 15 PET/CT studies of control age-matched subjects without signs or symptoms of vasculitis was also analyzed.

Results

Higher levels of regional and global FDG uptake were found at diagnosis in comparison with follow-up studies of 12 patients with complete longitudinal observation (p value range 0.0552–0.0026). In the latter group high values were generally observed when disease relapse or incomplete response to therapy (active disease) occurred, whereas lower uptake was found in studies of remitted patients (p = <0.01), whose FDG levels were similar to those of control subjects. At ROC analysis performed on all image dataset, optimal cut-off levels of regional and global FDG vascular uptake provided a good discrimination between 25 patients at diagnosis and 15 control subjects (aSUV greater than 0.697; PPV = 92.3; NPV = 92.9). Major overlap was observed among FDG levels of 21 patients with active disease and in remission (aSUV greater than 0.653; PPV = 58.3; NPV = 94.1). Similar performances of visual and semiquantitative analyses were found when areas under curves (AUCs) were compared.

Conclusions

¹⁸F-FDG PET/CT has a promising role in grading inflammation in patients with large arteries vasculitis. Nevertheless, a cut-off based analysis of FDG vascular uptake is not sufficient to separate patients with active and inactive disease during follow-up.

     

Respiratory-gated time-of-flight PET/CT during whole-body scan for lung lesions: feasibility in a routine clinical setting and quantitative analysis

Purpose

To demonstrate the feasibility of respiratory gating during whole-body scan for lung lesions in routine ¹⁸F-FDG PET/CT examinations using a time-of-flight (TOF)-capable scanner to determine the effect of respiratory gating on reduction of both misregistration (between CT and PET) and image blurring, and on improvement of the maximum standardized uptake value (SUVmax).

Materials and methods

Patients with lung lesions who received FDG PET/CT were prospectively studied. Misregistration, volume of PET (Vp), and SUVmax were compared between ungated and gated images. The difference in respiratory gating effects was compared between lesions located in the upper or middle lobes (UML) and the lower lobe (LL). The correlation between three parameters (% change in misregistration, % change in Vp, and lesion size) and % change in SUVmax was analyzed.

Results

The study population consisted of 60 patients (37 males, 23 females; age 68 ± 12 years) with lung lesions (2.5 ± 1.7 cm). Fifty-eight out of sixty respiratory gating studies were successfully completed with a total scan time of 20.9 ± 1.9 min. Eight patients’ data were not suitable for analysis, while the remaining 50 patients’ data were analyzed. Respiratory gating reduced both misregistration by 21.4 % (p < 0.001) and Vp by 14.2 % (p < 0.001). The SUVmax of gated images improved by 14.8 % (p < 0.001). The % change in misregistration, Vp, and SUVmax by respiratory gating tended to be larger in LL lesions than in UML lesions. The correlation with % change in SUVmax was stronger in % change in Vp (r = 0.57) than % change in misregistration (r = 0.35). There was no statistically significant correlation between lesion size and % change in SUVmax (r = ?0.20).

Conclusions

Respiratory gating during whole-body scan in routine TOF PET/CT examinations is feasible and can reduce both misregistration and PET image blurring, and improve the SUVmax of lung lesions located primarily in the LL.

     

Evaluating the Predictive Ability of Initial Staging F-18 FDG PET/CT for the Prognosis of Non-Hodgkin Malignant Lymphoma Patients Who Underwent Stem Cell Transplantation

Objectives

This study aimed to determine the value of clinical prognostic factors and semiquantitative metabolic parameters from initial staging fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) in non-Hodgkin lymphoma (NHL) patients treated with stem cell transplantation (SCT).

Methods

A total of 39 malignant lymphoma patients who underwent initial staging F-18 FDG PET/CT were enrolled in this study. SUVmax, MTV_wb, and TLG_wb were measured during the initial staging PET/CT. Receiver operating characteristic curve (ROC) analysis was adopted to dichotomize continuous variables. Log-rank test and Cox proportional hazard regression analysis were used to evaluate disease-free survival (DFS) rate.

Results

Among the 39 patients with malignant lymphoma, 17 (43.6%) had a relapse. For several clinical factors such as age, ECOG performance score, AMC/ALC score, stages, and revised International Prognostic Index score, differences between the two dichotomized groups were statistically insignificant. In univariate analysis, DFS estimates were 71.0 ± 7.8 months and 18.0 ± 5.9 months in high-SUVmax and low-SUVmax group, respectively (P < 0.01). For MTV_wb, DFS estimates were 46.6 ± 12.4 months and 69.1 ± 8.5 months in high-MTV_wb and low-MTV_wb group, respectively (P = 0.12). For TLG_wb, DFS estimates were 65.3 ± 7.5 months and 13.7 ± 8.6 months in high-TLG_wb and low-TLG_wb group, respectively (P = 0.02). In Cox proportional hazard regression analysis, only MTV_wb showed statistical significance (HR 3.01, 95% CI 1.04–8.74, P = 0.04).

Conclusion

In NHL patients treated with SCT, the MTV_wb of initial staging F-18 FDG PET/CT was an independent prognostic factor.