The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on Physiologic Myocardial 18F-FDG Uptake in Normal Humans

Purpose

In a whole-body ¹⁸F-FDG PET/CT, non-specific ¹⁸F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial ¹⁸F-FDG uptake.

Methods

F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before ¹⁸F-FDG injection from all subjects. Myocardial ¹⁸F-FDG uptake was measured as the mean (SUVmean) and maximal (SUVmax) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI). We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI).

Results

Overall, 92 subjects (mean age 50.28 ± 8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUVmax was 4.57, respectively and there was a strong linear correlation between SUVmean and SUVmax (r = 0.98). FFA and fasting duration showed significant negative correlation with myocardial ¹⁸F-FDG uptake, respectively (r = −0.40 in FFA; r = −0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI.

Conclusion

Myocardial ¹⁸F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve ¹⁸F-FDG PET/CT imaging for specific oncologic and cardiovascular indications.     

Association Between <Superscript>18</Superscript>F-FDG Avidity and the BRAF Mutation in Papillary Thyroid Carcinoma

Purpose

The BRAF mutation, a potential prognostic factor in papillary thyroid carcinoma (PTC), is associated with a high expression of the glucose transporter gene. We investigated which clinicopathologic factors, including BRAF mutation status, influence ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG) avidity.

Methods

We retrospectively reviewed 55 patients who underwent BRAF analysis from biopsy-confirmed PTC and ¹⁸F-FDG positron emission tomography/computed tomography within 6 months before undergoing thyroid surgery from September 2008 to August 2014. Tumors were considered to be ¹⁸F-FDG avid if the uptake was greater than that of the liver. ¹⁸F-FDG uptake of PTCs was also analyzed semiquantitatively using SUV_max. The association between ¹⁸F-FDG avidity and clinicopathologic variables (age, tumor size, perithyroidal extension, cervical lymph node status, and BRAF mutation status) was investigated.

Results

Twenty-nine (52.7 %) of 55 patients had ¹⁸F-FDG-avid PTCs. PTCs with the BRAF mutation showed higher ¹⁸F-FDG avidity (24/38, 63.2 %) than those without (5/17, 29.4 %). The BRAF mutation (p = 0.025) and tumor size (p = 0.003) were significantly associated with ¹⁸F-FDG avidity in univariate analysis, and the BRAF mutation status remained significant after adjusting for tumor size in multivariate analysis (p = 0.015). In the subgroup of tumor size ≥ 1 cm, the BRAF mutation was the only factor significantly associated with ¹⁸F-FDG avidity (p = 0.021). The mean SUV_max of PTCs with the BRAF mutation was significantly higher than that of those without (4.89 ± 6.12 vs. 1.96 ± 1.10, p = 0.039).

Conclusions

The BRAF mutation must be one of the most important factors influencing ¹⁸F-FDG avidity in PTCs, especially in those with a tumor size ≥ 1 cm.     

Usefulness of Combined Metabolic–Volumetric Indices of 18F-FDG PET/CT for the Early Prediction of Neoadjuvant Chemotherapy Outcomes in Breast Cancer

Purpose

The purpose of this study was to investigate the usefulness of metabolic-volumetric indices of ¹⁸F- fluorodeoxy-D-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) for the evaluation of neoadjuvant chemotherapy outcomes in breast cancer.

Methods

Twenty-four patients with locally advanced breast cancer were enrolled in the study. They underwent baseline ¹⁸F-FDG PET/CT scan and received four or six cycles of neoadjuvant chemotherapy, interim ¹⁸F-FDG PET/CT was done after second cycle of chemotherapy. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary lesions were calculated. Reduction rates of these parameters were obtained between baseline and interim ¹⁸F-FDG PET/CT. Chemotherapy outcomes were assessed using tumor size reduction rate and histological grading system (Miller and Payne system). Reduction rates of SUVmax, MTV, and TLG correlated with chemotherapy outcomes.

Results

MTV and TLG reduction rates showed significant correlation with tumor size reduction rate (R = 0.68, P = 0.0004; R = 0.62, P = 0.002, respectively). However, SUVmax reduction rate showed no significant correlation. MTV and TLG reduction rates were significantly higher in responders than nonresponders, as determined by Miller and Payne system (P < 0.0007, P < 0.002). However, SUVmax reduction rate showed no significant difference. On ROC analysis, the area under the MTV and TLG curves was 0.886, and that of SUVmax was 0.743. Sensitivity, specificity, positive predictive value, and negative predictive value to predict histopathologic response were the same for MTV and TLG, and the values were 100 %, 85.7 %, 83.3 %, and 100 %, respectively (at the reduction rate of 93.2 % for MTV, and 95.8 % for TLG).

Conclusion

Changes of metabolic–volumetric indices successfully reflected the neoadjuvant chemotherapy outcomes. MTV and TLG could be robust indices in discriminating pathologic responder as SUVmax, after neoadjuvant chemotherapy.     

Increased Brainstem Serotonergic Transporter Availability in Adult Migraineurs: an [<Superscript>18</Superscript>F]FP-CIT PET Imaging Pilot Study

Purpose

Recent studies have proposed central serotonergic dysfunction as a major pathophysiology of migraine. We investigated serotonin transporter (SERT) availability in migraineurs using F-18-N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([¹⁸F]FP-CIT) positron emission tomography (PET).

Methods

Brain [¹⁸F]FP-CIT PET images were obtained in eight women with migraine during headache free phase and 12 healthy adult women, 120 min after injection of 185 MBq. Non-displaceable binding potential (BP_ND) of [¹⁸F]FP-CIT, which is an estimate of SERT availability, was calculated at the brainstem and compared with clinical parameters.

Results

BP_ND at the brainstem was significantly higher in adult migraineurs (n = 6, 1.15 ± 0.17) than healthy subjects (0.95 ± 0.14) (p = 0.04). Healthy subjects demonstrated negative correlation between brainstem BP_ND and age (r = −0.64, p = 0.02), whereas this age-related decline pattern was not found in the migraineurs. Severity of migraine attack was significantly correlated with brainstem BP_ND (r = 0.66, p = 0.02), when age and duration of illness were corrected.

Conclusions

Increased SERT availability in the brainstem of adult migraineurs indicates low serotonin neurotransmission during headache-free phase. Patients who experience more painful headaches have lower serotonin neurotransmission. [¹⁸F]FP-CIT PET is a useful in vivo imaging technique for evaluating brainstem SERT availability in migraineurs.     

Prognostic Value of Volume-Based Metabolic Parameters Measured by 18F-FDG PET/CT of Pancreatic Neuroendocrine Tumors

Purpose

To date, the prognostic value of ¹⁸F-FDG PET/CT for patients with pancreatic neuroendocrine tumors (PNETs) has not been well characterized. We investigated the prognostic value of volumetric parameters using ¹⁸F-FDG PET/CT in this patient population.

Methods

We retrospectively reviewed 20 cases of pathologically proven PNET in patients who had undergone pre-therapeutic ¹⁸F-FDG PET/CT. PET parameters including maximum and average standardized uptake values (SUV_max, SUV_ave), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were measured using a threshold SUV to determine the boundaries of the tumors. Univariate and multivariate survival analyses were performed with adjustments for PET parameters and other clinical values.

Results

The median clinical follow-up was 22.3 (range, 1.2–95.4) months. Cancer-related death occurred in 5 of 20 patients (25 %). Patients had clinical or pathological stages of I in seven patients, II in six patients, III in three patient, and IV in four patients. According to the WHO histological classification of subtypes, 3 patients exhibited well-differentiated PNETs, 13 patients had well-differentiated endocrine carcinomas, and 4 had poorly differentiatedendocrine carcinomas. Univariate analysis showed that tumor size (p = 0.028), AJCC stage (p = 0.009), T stage (p = 0.028), M stage (p = 0.029), treatment modality (p = 0.045), MTV (p = 0.003) and TLG (p = 0.027) were significant predictors of overall survival. On multivariate analysis, MTV (HR = 10.859, p = 0.031) was a significant independent predictor of overall survival along with the AJCC stage (HR = 11.556, p = 0.027).

Conclusion

In patients with PNETs, the MTV of the primary tumor as measured by ¹⁸F-FDG PET/CT along with the AJCC stage may be a significant independent prognostic factor for overall survival.     

Incidental Focal 18F-FDG Uptake in the Prostate: Clinical Significance and Differential Diagnostic Criteria

Purpose

The extent and intensity of ¹⁸F-FDG uptake in prostate cancer patients are known to be variable, and the clinical significance of focal ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) uptake that is incidentally found on positron emission tomography (PET) has not been established. We investigated the clinical significance of incidental focal prostate uptake of ¹⁸F-FDG on PET/computed tomography (CT) and analyzed differential findings on PET/CT between malignant and benign uptake.

Methods

A total of 14,854 whole-body ¹⁸F-FDG PET/CT scans (4,806 that were conducted during cancer screening and 10,048 that were conducted to evaluate suspected or alleged cancer outside of the prostate) were retrospectively reviewed to determine the presence, location, multiplicity and maximum standardized uptake value (SUVmax) of focal prostate uptake and combined calcification. The final diagnosis determined by serum prostate-specific antigen (PSA) level and biopsy was compared with PET findings.

Results

Incidental focal prostate uptake was observed in 148 of 14,854 scans (1.0 %). Sixty-seven of these 148 subjects who had diagnostic confirmation were selected for further analysis. Prostate cancer was diagnosed in nine of 67 subjects (13.4%). The remaining 58 subjects had no malignancy in the prostate based on normal serum PSA level (n = 53), or elevated serum PSA level with a negative biopsy result (n = 5). While 84.6% (11/13) of malignant uptake was peripherally located in the prostate glands, 60.2% (50/83) of benign uptake was centrally located (p < 0.05). The positive predictive value of peripheral focal uptake for malignancy was 25%. The SUVmax, multiplicity and combined calcification were not significantly different between the two groups.

Conclusion

Although incidental focal ¹⁸F-FDG uptake in the prostate is not common, the incidence of cancer with focal uptake is not low. Therefore, these findings deserve further evaluation. The location of the focal prostate uptake may help with the selection of high-risk prostate cancer patients.     

18F-FDG Uptake of Human Testis on PET/CT: Correlation with Age,Sex Hormones,and Vasectomy

Purpose

The purpose of this study was to evaluate glucose metabolism of normal human testis on ¹⁸F-FDG PET/CT and to assess possible correlations among age, the serum levels of sex hormones, and vasectomy.

Methods

¹⁸F-FDG PET/CT was performed in 66 normal healthy men (50.8 ± 13.6 years, range 22–81), and mean standard uptake values (SUV) of ¹⁸F-FDG in testis and adductor muscle were measured. Testis-muscle SUV ratios (T/M ratios) were calculated. Serum levels of total testosterone, free testosterone, estradiol, and of sex-hormone binding globulin (SHBG) were measured. We searched for correlations between T/M ratios and age and the serum concentrations of sex hormones. ¹⁸F-FDG PET/CT was also performed in 32 vasectomized men (55.7 ± 7.8 years, range 38–71) and 52 nonvasectomized men (55.4 ± 11.6 years, range 37–72). Mean SUVs of testis and adductor muscle were measured, and T/M ratios were calculated.

Results

A significant age-related decline was found in T/M ratio (r = −0.509, p < 0.0001). Serum levels of total testosterone and free testosterone were also found to be positively correlated with T/M ratio (r = 0.427, p = 0.0003; r = 0.435, p = 0.0003, respectively). The mean SUV and T/M ratio of vasectomized men were significantly lower than those of nonvasectomized men (p < 0.0378 and p = 0.0001, respectively).

Conclusions

Glucose metabolism in the testis in an adult population was found to be correlated with age, serum sex hormone level, and vasectomy history. These results indicate that testicular ¹⁸F-FDG uptake may have attributed to testicular function and testicular histology. Our findings may have important implications for the interpretation of testicular ¹⁸F-FDG uptake in the normal adult population.     

Dynamic 18 F-FDG PET for Assessment of Tumor Physiology in Two Breast Carcinoma Xenografts

Purpose

To compare dynamic 2-deoxy-2-[¹⁸ F]fluoro-D-glucose positron emission tomography (¹⁸ F-FDG PET) parameters in two selected human breast cancer xenografts and to evaluate associations with immunohistochemistry and histology.

Procedures

Dynamic ¹⁸ F-FDG PET of luminal-like MAS98.06 and basal-like MAS98.12 xenografts was performed, and the compartmental transfer rates (k₁,k₂,k₃), blood volume fraction (v_B) and metabolic rate of ¹⁸ F-FDG(MR_FDG) were estimated from pharmacokinetic model analysis. After sacrifice, analyses of hypoxia (pimonidazole), proliferation (Ki-67), vascularization (CD31), glucose transport receptor (GLUT1) and necrosis (HE) was performed. The level of hexokinase 2 (HK2) was estimated from Western blot analysis.

Results

The ¹⁸ F-FDG uptake curves for the two xenografts were significantly different (p < 0.05). k₁ and v_B were higher for MAS98.12 (p < 0.01), while k₃ was higher for MAS98.06 (p < 0.01). MAS98.12 had a higher fraction of stromal tissue and higher microvessel density (MVD), and it was less necrotic and hypoxic than MAS98.06. MAS98.12 had stronger positive GLUT1 staining and lower Ki-67 than MAS98.06. In both models significant correlations were found between k₁ and the GLUT1 score, between k₃ and the level of HK2, and between v_B and MVD.

Conclusions

Significant differences in dynamic ¹⁸ F-FDG parameters between the two human breast cancer xenografts were found. The differences could be explained by underlying histological and physiological characteristics.     

18F-FDG PET/CT is Useful for Pretreatment Assessment of the Histopathologic Type of Thymic Epithelial Tumors

Purpose

This study was performed to assess the usefulness of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) or PET/computed tomography (CT) for distinguishing thymic epithelial tumors according to World Health Organization (WHO) classifications.

Methods

We analyzed a total of 45 patients (range, 29–75 years of age; mean, 55 years) with pathologically confirmed thymic epithelial tumors who underwent pretreatment ¹⁸F-FDG PET or PET/CT between November 2003 and October 2009. The size, visual grading of uptake value, peak standardized uptake value (SUVpeak), uptake pattern, and contour of each tumor, and associated findings on PET or PET/CT, were analyzed relative to the three simplified WHO subgroups: less-invasive thymomas (types A and AB), more-invasive thymomas (types B1, B2, and B3) and thymic carcinomas. We statistically assessed the relationship of ¹⁸F-FDG PET or PET/CT findings with these simplified subgroups.

Results

Of the 45 patients, ten had less-invasive thymomas, 23 had more-invasive thymomas, and 12 had thymic carcinomas. The SUVpeak of the less- and more-invasive thymomas were significantly lower than those of thymic carcinomas (p < 0.000), but there was no difference in SUVpeak between less- and more-invasive thymomas. The visual grading scale (p < 0.000), uptake pattern (p = 0.001), and contour (p < 0.000) of the tumors differed significantly among the three simplified subgroups.

Conclusion

The image findings of ¹⁸F-FDG PET or PET/CT differed significantly by histologic subgroups. Pre-treatment evaluation with ¹⁸F-FDG PET or PET/CT might be helpful in differentiating subgroups of thymic epithelial tumors.     

Relations Between Pathological Markers and Radioiodine Scan and 18F-FDG PET/CT Findings in Papillary Thyroid Cancer Patients With Recurrent Cervical Nodal Metastases

Purpose

The aim of this study was to investigate relationships between the immunohistochemical results and radioiodine scan and ¹⁸F-FDG PET findings in papillary thyroid cancer (PTC) patients with recurrent cervical nodal metastases.

Methods

A total of 46 PTC patients who had undergone a radioiodine scan and/or ¹⁸F-FDG PET/CT and a subsequent operation on recurrent cervical lymph nodes were enrolled. Twenty-seven patients underwent ¹⁸F-FDG PET/CT, 8 underwent radioiodine scans, and 11 underwent both scans. In all surgical specimens, the immunoexpressions of thyroglobulin (Tg), sodium-iodide symporter (NIS), glucose transporter 1 (Glut-1), and somatostatin receptor 1 and 2A (SSTR1 and SSTR2A) were assessed, and associations between these expressions and radioiodine scan and ¹⁸F-FDG PET findings were evaluated.

Results

Of the 38 patients who underwent ¹⁸F-FDG PET/CT, all patients with weak Tg expression had positive ¹⁸F-FDG uptake, while only 45 % of the patients with moderate or strong Tg expression showed positive uptake (p = 0.01). The proportion of patients with positive ¹⁸F-FDG uptake increased as the degree of Glut-1 expression with luminal accentuation increased. Of the 19 patients who underwent a radioiodine scan, the proportion with positive radioiodine uptake was greater among patients with strong NIS and SSTR2A expression than among patients expressing these markers at weak levels (p = 0.04 for all). All three patients with weak Tg expression were negative for radioiodine uptake.

Conclusion

The ¹⁸F-FDG uptakes of recurrent cervical nodes are related to strong Glut-1 expression with luminal accentuation and weak Tg expression, whereas radioiodine uptake is related to the strong expressions of NIS and SSTR2A.     

Heterogeneity Analysis of 18F-FDG Uptake in Differentiating Between Metastatic and Inflammatory Lymph Nodes in Adenocarcinoma of the Lung: Comparison with Other Parameters and its Application in a Clinical Setting

Purpose

Lymph node (LN) characterization is crucial in determining the stage and treatment decisions in patient with lung cancer. Although ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) has a higher diagnostic accuracy in LN characterization than anatomical imaging, differentiating between metastatic and inflammatory LNs is still challenging because both could show high ¹⁸F-FDG uptake. The purpose of this study was to assess if the heterogeneity of the ¹⁸F-FDG uptake could help in differentiating between inflammatory and metastatic LNs in lung cancer, and to compare with other parameters.

Methods

A total of 44 patients with adenocarcinoma of the lung, who underwent preoperative ¹⁸F-FDG PET/CT without having any previous treatments and were revealed to have ¹⁸F-FDG-avid LNs, were enrolled. There were 52 pathology-proven metastatic lymph nodes in 26 subjects. The pathology-proven metastatic LNs were compared with 42 pathology-proven inflammatory/benign LNs in 18 subjects. The coefficient of variation (CV) was used to assess the heterogeneity of ¹⁸F-FDG uptake by dividing the standard deviation of standardized uptake value (SUV) by mean SUV. The volume of interest was manually drawn based on the combined CT images of ¹⁸F-FDG PET/CT (no threshold is used). Comparisons were made with the maximum standardized uptake values (SUVmax), visual assessment of ¹⁸F-FDG uptake, longest diameter, and maximum Hounsfield units (HUmax).

Results

Metastatic lymph nodes tended to have higher CVs than the inflammatory LNs. The mean CV of metastatic LNs (0.30 ± 0.08; range: 0.08–0.55) was higher than that of inflammatory LNs (0.17 + 0.06; range, 0.07–0.32; P < 0.0001). On receiver operating characteristic (ROC) curve analysis, the area under curve was 0.901, and using 0.20 as cut-off value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 88.5 %, 76.2 %, 82.2 %, 84.3, and 83.0 % respectively. Accuracy of CV was slightly higher than SUVmax and diameter, but significantly higher than visual assessment and HUmax.

Conclusions

In patients with adenocarcinoma of the lung having no prior treatments, metastatic LNs showed more heterogeneous ¹⁸F-FDG uptake than inflammatory LNs. Measuring the CV of the SUV derived from a manual volume of interest (VOI) can be helpful in determining metastatic LN of adenocarcinoma of the lung. Including diagnostic criteria of CV into the diagnostic approach can increase the accuracy of mediastinal node status.     

Prognostic Value of SUVmax Measured by Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography with Computed Tomography in Patients with Gallbladder Cancer

Objective

The aim of this study is to investigate the prognostic value of F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) in gallbladder cancer patients.

Methods

From June 2004 to June 2010, a total of 50 patients with gallbladder cancer who underwent diagnostic staging with F-18 FDG PET/CT following curative or palliative treatments were retrospectively evaluated. For the analysis, all patients were classified by age, sex, maximum standardized uptake value (SUVmax), lymph node (LN) or distant metastasis, serum level of CA19-9 and CEA, type of treatment and American Joint Committee on Cancer (AJCC) stage.

Results

The median survival for the 50 patients was 245 days and the median SUVmax in PET/CT was 8.3 (range, 0-19.7). Patients with SUVmax < 6 survived significantly longer than patients with SUVmax ≥ 6 (median 405 days vs 203 days, p = 0.0400). On Kaplan-Meier analysis, SUVmax (p = 0.0400), stage (p = 0.0001), CA19-9 (p = 0.013), CEA (p = 0.006), LN metastasis (p = 0.0001), distant metastasis (p = 0.0020), type of treatment (p = 0.0001) were significantly associated with overall survival. Multivariate analysis study revealed that the patients with lower SUVmax measured from initial staging PET/CT (p = 0.0380), no LN metastasis (p = 0.0260), a lower stage (p = 0.026) and curative treatment (p = 0.0005) had longer survivals.

Conclusions

The present study shows that SUVmax on F-18 FDG PET/CT can provide prognostic information in patients with gallbladder cancer.     

The Prognostic Value of 18F-FDG PET/CT for Early Recurrence in Operable Breast Cancer: Comparison with TNM Stage

Purpose

We evaluated whether the maximum standardized uptake values (SUV_max) of primary tumor from the initial staging by ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) of patients with breast cancer could identify patients at risk for early recurrence within 2 years, particularly in comparison to the American Joint Committee on Cancer (AJCC) stage.

Methods

We reviewed the staging ¹⁸F-FDG PET/CT images of patients with primary breast cancer and their medical records. The SUV_max of the primary tumor was measured. The presence or absence of FDG uptake in the axillary lymph node (ALN) was also assessed. The patient’s pathologic primary tumor stage (pT), pathologic regional lymph node stage (pN), stage grouping, age, estrogen receptor (ER) and progesterone receptor (PR) status, and neoadjuvant chemotherapy history were evaluated with the FDG uptake parameters for recurrence within 2 years following the end of first-line therapy.

Results

Recurrence within 2 years was present in 9.1 % (n = 40) out of the 441 patients assessed. The FDG uptake in ALN, pT, pN, stage grouping and neoadjuvant chemotherapy history were prognostic for early recurrence, while primary tumor SUV_max, age, and ER or PR status were not significant on logistic regression. On multivariate analysis, only the stage grouping (odds ratio 2.79; 95 % CI 1.73, 4.48; p < 0.0001) and neoadjuvant chemotherapy history (odds ratio 2.70; 95 % CI 1.22, 5.98; p = 0.0141) could identify patients at increased risk for recurrence within 2 years.

Conclusions

Primary tumor FDG uptake measured by SUV_max, and visual assessment of FDG uptake in the ALN in the initial staging PET/CT of patients with breast cancer may not have additional prognostic value compared with the AJCC stage grouping for early recurrence.     

18F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma: Differential Features According to Expression of Anaplastic Lymphoma Kinase

Purpose

Primary systemic anaplastic large cell lymphoma (ALCL) is divided into two entities according to the expression of anaplastic lymphoma kinase (ALK). We investigated ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) findings in primary systemic ALCL according to ALK expression.

Methods

Thirty-seven patients who had baseline PET before CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based chemotherapy were enrolled. Among them, patients who underwent interim and/or post-therapy PET were further investigated for the treatment response and survival analysis. Baseline PET was analyzed visually and semi-quantitatively using peakSUV, and interim and post-therapy PETs were visually analyzed.

Results

All cases were ¹⁸F-FDG-avid on baseline PET. The peakSUV of ALK-positive ALCL (n = 16, 18.7 ± 10.5) was higher than that of ALK-negative ALCL (n = 21, 10.0 ± 4.9) (P = 0.006). In ALK-negative ALCL, complete response (CR) rate in negative-interim PET was higher than positive-interim PET (100 % vs 37.5 %, P = 0.02); however, there was no such difference in ALK-positive ALCL (100 % vs 75 %, P = 0.19). The 3-year progression-free survival (PFS) was not significantly different between ALK-positive and ALK-negative ALCL (72.7 % vs 47.6 %, P = 0.34). In ALK-negative ALCL, negative interim and post-therapy PET patients had better 3-year PFS than positive interim (83.3 % vs 25.0 %, P = 0.06) and post-therapy PET patients (70.0 % vs 20.0 %, P = 0.04). In contrast, ALK-positive ALCL had no such differences between PFS and PET results.

Conclusions

On baseline PET, all cases showed ¹⁸F-FDG-avidity, and ALK expression was related to higher ¹⁸F-FDG uptake. ALK-positive patients tend to have better PFS than ALK-negative patients. Negative-interim PET was a good indicator of CR, and interim or post-therapy PET was helpful for predicting the prognosis only in the ALK-negative group.     

The Role of 18 F-FDG PET/CT in Assessing Therapy Response in Cervix Cancer after Concurrent Chemoradiation Therapy

Purpose

To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy.

Methods

F-FDG PET/CT was performed before and after CCRT in 136 patients with cervical cancer. The maximum and mean standardized uptake values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and post-treatment. SUVs were correlated with treatment response after CCRT. Final treatment response was determined by MRI and further follow-up PET/CT. One hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients underwent further follow-up PET/CT. Patients were classified into two categories: patients with residual tumor or patients without residual tumor (complete responder). Pre- and post-treatment serum squamous cell carcinoma antigen (SCC) levels were also recorded for comparison. The optimal cutoff value of SUVmax for predicting residual cervical tumor was determined using receiver-operating characteristic (ROC) analysis.

Results

Of 136 patients, 124 showed complete response on further follow-up studies and 12 were confirmed to have residual tumor. The post-treatment SUVmax and pre-/post-treatment SUVmean of complete responders were significantly lower than those of patients with residual tumor: 2.5 ± 0.8 and 7.2 ± 4.2/1.9 ± 0.7 for complete responders and 5.7 ± 2.6 and 12.8 ± 6.9/3.7 ± 0.7 for patients with residual tumor (p < 0.05). The pre-treatment SUVmax and pre-/post-treatment serum SCC levels of the complete responders tended to be lower than those of patients with residual tumor, but this did not have statistical significance. Using ROC analysis, an optimal cutoff SUVmax of 4.0 on the post-treatment PET/CT yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 92 %, 94 %, 61 %, and 99 %, respectively (p < 0.001).

Conclusions

Persistent cervical FDG uptake in¹⁸F-FDG PET/CT after CCRT for cervical cancer may be caused by residual tumor or post-therapy inflammation. A higher cutoff SUVmax than conventional criteria for cervical cancer in post-CCRT PET/CT might help to detect residual tumor.     

Diagnostic Performance of 68Ga-DOTATATE PET/CT, 18F-FDG PET/CT and 131I-MIBG Scintigraphy in Mapping Metastatic Pheochromocytoma and Paraganglioma

Purpose

To evaluate the diagnostic performance of ⁶⁸Ga-DOTATATE ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT), ¹⁸F-FDG PET/CT and ¹³¹I-MIBG scintigraphy in the mapping of metastatic pheochromocytoma and paraganglioma.

Materials and Methods

Seventeen patients (male = 8, female = 9; age range, 13–68 years) with clinically proven or suspicious metastatic pheochromocytoma or paraganglioma were included in this prospective study. Twelve patients underwent all three modalities, whereas five patients underwent ⁶⁸Ga-DOTATATE and ¹³¹I-MIBG without ¹⁸F-FDG. A composite reference standard derived from anatomical and functional imaging findings, along with histopathological information, was used to validate the findings. Results were analysed on a per-patient and on per-lesion basis. Sensitivity and accuracy were assessed using McNemar’s test.

Results

On a per-patient basis, 14/17 patients were detected in ⁶⁸Ga-DOTATATE, 7/17 patients in ¹³¹I-MIBG, and 10/12 patients in ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (93.3 %, 94.1 %), (46.7 %, 52.9 %) and (90.9 %, 91.7 %) respectively. On a per-lesion basis, an overall of 472 positive lesions were detected; of which 432/472 were identified by ⁶⁸Ga-DOTATATE, 74/472 by ¹³¹I-MIBG, and 154/300 (patient, n = 12) by ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (91.5 %, 92.6 % p < 0.0001), (15.7 %, 26.0 % p < 0.0001) and (51.3 %, 57.8 % p < 0.0001) respectively. Discordant lesions were demonstrated on ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG.

Conclusions

Ga-DOTATATE PET/CT shows high diagnostic accuracy than ¹³¹I-MIBG scintigraphy and ¹⁸F-FDG PET/ CT in mapping metastatic pheochromocytoma and paraganglioma.     

Imaging Findings and Literature Review of 18F-FDG PET/CT in Primary Systemic AL Amyloidosis

Purpose

Although several case reports and case series have described ¹⁸F-FDG PET/CT in amyloidosis, the value of ¹⁸F-FDG PET/CT for diagnosing amyloidosis has not been clarified. We investigated the imaging findings of ¹⁸F-FDG PET/CT in patients with primary systemic AL amyloidosis.

Methods

Subjects were 15 patients (M:F = 12:3; age, 61.5 ± 7.4 years) with histologically confirmed primary systemic AL amyloidosis who underwent pretreatment ¹⁸F-FDG PET/CT to rule out the possibility of malignancy or for initial workup of alleged cancer. For involved organs, visual and semiquantitative analyses were performed on ¹⁸F-FDG PET/CT images. In total, 22 organs (10 hearts, 5 kidneys, 2 stomachs, 2 colons, 1 ileum, 1 pancreas, and 1 liver) were histologically confirmed to have primary systemic AL amyloidosis.

Results

F-FDG uptake was significantly increased in 15 of the 22 organs (68.2 %; 10 hearts, 2 kidneys, 1 colon, 1 ileum, and 1 liver; SUVmax = 7.0 ± 3.2, range 2.1–14.1). However, in 11 of 15 PET-positive organs (78.6 %; 10 hearts and the ileum), it was difficult to differentiate pathological uptake from physiological uptake. Definitely abnormal ¹⁸F-FDG uptake was found in only 4 of the 22 organs (18.2 %; 2 kidneys, 1 colon, and the liver). ¹⁸F-FDG uptake was negative for pancreas and gastric lesions.

Conclusions

Although ¹⁸F-FDG PET/CT showed high uptake in two-thirds of the organs involving primary systemic AL amyloidosis, its sensitivity appeared to be low to make differentiation of pathological uptake from physiological uptake. However, due to the small number of cases, further study for the role of ¹⁸F-FDG PET/CT in amyloidosis will be warranted.     

Comparison between 18F-FDG PET/CT and EMG Mapping for Identifying Dystonic Superficial Muscles in Primary Cervical Dystonia: Preliminary Results

Purpose

This study was conducted to compare ¹⁸F-FDG PET/CT and electromyography (EMG) mapping in patients with primary cervical dystonia (PCD) to find dystonic superficial cervical muscles.

Methods

Ten consecutive patients with PCD (M:F = 5:5, age 44 ± 13 years) whose dystonic posture was not relieved with conventional muscle relaxant therapy were included. Target cervical muscles for the comparison between ¹⁸F-FDG PET/CT and EMG mapping were four representative superficial bilateral cervical muscles: splenius capitis muscle, sternocleidomstoid muscle, upper trapezius muscle, and leavator scapulae muscle. The diagnostic efficacy was compared between ¹⁸F-FDG PET/CT and EMG mapping using physical exam and measurement of rotation angle as the gold standard.

Results

Among 80 muscles evaluated, there were 21 (26%) dystonic superficial cervical muscles assessed with physical exam and motion analysis. The sensitivity, specificity, and accuracy for localizing dystonic muscles were 76, 92, and 88% for ¹⁸F-FDG PET/CT, and 95, 66, and 74% for EMG mapping, respectively. The sensitivity of EMG mapping was significantly higher than that of ¹⁸F-FDG PET/CT. In contrast, ¹⁸F-FDG PET/CT was significantly superior to EMG mapping for specificity and accuracy.

Conclusions

¹⁸F-FDG PET/CT is more specific and accurate than EMG mapping for finding superficial dystonic cervical muscles. The high sensitivity of EMG mapping suggests that ¹⁸F-FDG PET/CT and EMG mapping are complementary for finding dystonic superficial cervical muscles.     

Detection and Characterization of Parathyroid Adenoma/Hyperplasia for Preoperative Localization: Comparison Between 11C-Methionine PET/CT and 99mTc-Sestamibi Scintigraphy

Purpose

¹¹C-Methionine PET/CT (Met-PET/CT) is a useful imaging method for detection of parathyroid adenoma; however, the reported detection rate has been variable. The current study was intended to investigate detection sensitivity and preoperative localization of parathyroid adenoma (PA) or parathyroid hyperplasia (PH) on Met-PET/CT compared with ^99mTc-sestamibi (MIBI) scintigraphy in patients with primary hyperparathyroidism (HPT) or suspected PA.

Methods

Met-PET/CT and MIBI scintigraphy images were reviewed by two nuclear medicine physicians unaware of pathologic results. Detection sensitivities and preoperative localization of detected parathyroid tissues into five predefined segments were evaluated by visual assessment and semi-quantitative analysis with ratio of standardized uptake values (SUVR) between parathyroid tissue and normal lung as reference. Linear regression analysis with SUVR and serum parathyroid hormone (sPTH) was performed for characterization of PA or PH. Predicted PTH (pPTH) was calculated and compared with sPTH in PH and PA. Each pPTH was obtained for a calculated SUVR by using linear regression model from the result of previous linear regression analysis between SUVR and sPTH.

Results

In 16 patients, detection sensitivities of Met-PET/CT and MIBI scintigraphy were 91.7 % (11/12) and 41.7 % (5/12) for PA and PH including both biopsy-confirmed and clinically-suspected cases, and 100 % (8/8) and 50 % (4/8) for pathologically confirmed PA and PH cases only, respectively. Met-PET/CT showed higher performance than MIBI scintigraphy in localization of parathyroid tissues; correct localization rate was 87.5 % (7/8) on Met-PET/CT and 50 % (4/8) on MIBI scintigraphy. In semi-quantitative analysis, SUVR was linearly associated with sPTH by linear regression analysis (sPTH = 39.53 × SUVR − 89.84, p = 0.0383). There was a borderline significant difference in pPTH between PH and PA (35.1 vs 204.7 ± 164.0, p = 0.052), while there was no significant difference in sPTH between PH and PA (289 vs 230.4 ± 160.4, p = 0.305).

Conclusions

Met-PET/CT has a potential to be a useful diagnostic modality for preoperative detection and localization of parathyroid tissues with higher sensitivity than MIBI scintigraphy, and for characterization of PA or PH.     

<Superscript>18</Superscript>F-FDG uptake by rectal cancer is similar in mucinous and nonmucinous histological subtypes

Purpose

PET/CT has been considered limited for the evaluation of mucinous colorectal tumors due to low ¹⁸F-FDG uptake. The aim of our study was to compare PET/CT variables in mucinous (MC) and nonmucinous (NMC) rectal adenocarcinomas.

Methods

Consecutive patients with cT2-4N0-2M0 rectal cancer included in a prospective clinical trial were reviewed. PET/CT was performed for primary baseline staging. Visual and quantitative analysis included SUVmax and SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). PET/CT parameters were compared according to histological subtypes.

Results

Overall, 73 patients were included (18 mucinous and 55 nonmucinous). SUVmax values were similar between MC and NMC (19.7 vs. 16.6; p = 0.5). MTV and TLG values were greater in the MC group (103.9 vs. 54.1; p = 0.007 and 892.5 vs. 358.8; p = 0.020) due to larger tumor volumes of MC.

Conclusions

Metabolic parameters at baseline PET/CT for patients with rectal cancer are similar in mucinous and nonmucinous histological subtypes.