18F-FDG PET/CT for detection of malignant peripheral nerve sheath tumours in neurofibromatosis type 1: tumour-to-liver ratio is superior to an SUVmax cut-off

Objectives

To evaluate the usefulness of normalising intra-tumour tracer accumulation on ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to reference tissue uptake for characterisation of peripheral nerve sheath tumours (PNSTs) in neurofibromatosis type 1 (NF1) compared with the established maximum standardised uptake value (SUVmax) cut-off of >3.5.

Methods

Forty-nine patients underwent FDG PET/CT. Intra-tumour tracer uptake (SUVmax) was normalised to three different reference tissues (tumour-to-liver, tumour-to-muscle and tumour-to-fat ratios). Receiver operating characteristic (ROC) analyses were used out to assess the diagnostic performance. Histopathology and follow-up served as the reference standard.

Results

Intra-tumour tracer uptake correlated significantly with liver uptake (r _s ?=?0.58, P?=?0.016). On ROC analysis, the optimum threshold for tumour-to-liver ratio was >2.6 (AUC?=?0.9735). Both the SUVmax cut-off value of >3.5 and a tumour-to-liver ratio >2.6 provided a sensitivity of 100 %, but specificity was significantly higher for the latter (90.3 % vs 79.8 %; P?=?0.013).

Conclusions

In patients with NF1, quantitative ¹⁸F-FDG PET imaging may identify malignant change in neurofibromas with high accuracy. Specificity could be significantly increased by using the tumour-to-liver ratio. The authors recommend further evaluation of a tumour-to-liver ratio cut-off value of >2.6 for diagnostic intervention planning.

Key Points

? ¹⁸ F-FDG PET/CT is used for detecting malignancy in PNSTs in NF1 patients ? An SUV _max cut-off value may give false-positive results for benign plexiform neurofibromas ? Specificity can be significantly increased using a tumour-to-liver ratio     

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.     

The value of intratumoral heterogeneity of 18F-FDG uptake to differentiate between primary benign and malignant musculoskeletal tumours on PET/CT

Objective:

The cumulative standardized uptake value (SUV)–volume histogram (CSH) was reported to be a novel way to characterize heterogeneity in intratumoral tracer uptake. This study investigated the value of fluorine-18 fludeoxyglucose (¹⁸F-FDG) intratumoral heterogeneity in comparison with SUV to discriminate between primary benign and malignant musculoskeletal (MS) tumours.

Methods:

The subjects comprised 85 pathologically proven MS tumours. The area under the curve of CSH (AUC-CSH) was used as a heterogeneity index, with lower values corresponding with increased heterogeneity. As 22 tumours were indiscernible on ¹⁸F-FDG positron emission tomography, maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean) and AUC-CSH were obtained in 63 positive tumours. The Mann–Whitney U test and receiver operating characteristic (ROC) analysis were used for analyses.

Results:

The difference between benign (n = 35) and malignant tumours (n = 28) was significant in AUC-CSH (p = 0.004), but not in SUV_max (p = 0.168) and SUV_mean (p = 0.879). The sensitivity, specificity and accuracy for diagnosing malignancy were 61%, 66% and 64% for SUV_max (optical threshold value, >6.9), 54%, 60% and 57% for SUV_mean (optical threshold value, >3) and 61%, 86% and 75% for AUC-CSH (optical threshold value, ≤0.42), respectively. The area under the ROC curve was significantly higher in AUC-CSH (0.71) than SUV_max (0.60) (p = 0.018) and SUV_mean (0.51) (p = 0.005).

Conclusion:

The heterogeneity index, AUC-CSH, has a higher diagnostic accuracy than SUV analysis in differentiating between primary benign and malignant MS tumours, although it is not sufficiently high enough to obviate histological analysis.

Advances in knowledge:

AUC-CSH can assess the heterogeneity of ¹⁸F-FDG uptake in primary benign and malignant MS tumours, with significantly greater heterogeneity associated with malignant MS tumours. AUC-CSH is more diagnostically accurate than SUV analysis in differentiating between benign and malignant MS tumours.     

Anatomical and functional volume concordance between FDG PET,and T2 and diffusion-weighted MRI for cervical cancer: a hybrid PET/MR study

Purpose

To evaluate the concordance among ¹⁸F-FDG PET imaging, MR T2-weighted (T2-W) imaging and apparent diffusion coefficient (ADC) maps with diffusion-weighted (DW) imaging in cervical cancer using hybrid whole-body PET/MR.

Methods

This study prospectively included 35 patients with cervical cancer who underwent pretreatment ¹⁸F-FDG PET/MR imaging. ¹⁸F-FDG PET and MR images were fused using standard software. The percent of the maximum standardized uptake values (SUV_max) was used to contour tumours on PET images, and volumes were calculated automatically. Tumour volumes measured on T2-W and DW images were calculated with standard techniques of tumour area multiplied by the slice profile. Parametric statistics were used for data analysis.

Results

FDG PET tumour volumes calculated using SUV_max (14.30?±?4.70) and T2-W imaging volume (33.81?±?27.32 cm³) were similar (P?>?0.05) at 35 % and 40 % of SUV_max (32.91?±?18.90 cm³ and 27.56?±?17.19 cm³ respectively) and significantly correlated (P?<?0.001; r?=?0.735 and 0.766). The mean DW volume was 30.48?±?22.41 cm³. DW volumes were not significantly different from FDG PET volumes at either 35 % SUV_max or 40 % SUV_max or from T2-W imaging volumes (P?>?0.05). PET subvolumes with increasing SUV_max cut-off percentage showed an inverse change in mean ADC values on DW imaging (P?<?0.001, ANOVA).

Conclusion

Hybrid PET/MR showed strong volume concordance between FDG PET, and T2-W and DW imaging in cervical cancer. Cut-off at 35 % or 40 % of SUV_max is recommended for ¹⁸F-FDG PET/MR SUV-based tumour volume estimation. The linear tumour subvolume concordance between FDG PET and DW imaging demonstrates individual regional concordance of metabolic activity and cell density.     

Detection and quantification of focal uptake in head and neck tumours: 18F-FDG PET/MR versus PET/CT

Purpose

Our objectives were to assess the quality of PET images and coregistered anatomic images obtained with PET/MR, to evaluate the detection of focal uptake and SUV, and to compare these findings with those of PET/CT in patients with head and neck tumours.

Methods

The study group comprised 32 consecutive patients with malignant head and neck tumours who underwent whole-body ¹⁸F-FDG PET/MR and PET/CT. PET images were reconstructed using the attenuation correction sequence for PET/MR and CT for PET/CT. Two experienced observers evaluated the anonymized data. They evaluated image and fusion quality, lesion conspicuity, anatomic location, number and size of categorized (benign versus assumed malignant) lesions with focal uptake. Region of interest (ROI) analysis was performed to determine SUVs of lesions and organs for both modalities. Statistical analysis considered data clustering due to multiple lesions per patient.

Results

PET/MR coregistration and image fusion was feasible in all patients. The analysis included 66 malignant lesions (tumours, metastatic lymph nodes and distant metastases), 136 benign lesions and 470 organ ROIs. There was no statistically significant difference between PET/MR and PET/CT regarding rating scores for image quality, fusion quality, lesion conspicuity or anatomic location, number of detected lesions and number of patients with and without malignant lesions. A high correlation was observed for SUV_mean and SUV_max measured on PET/MR and PET/CT for malignant lesions, benign lesions and organs (ρ?=?0.787 to 0.877, p?<?0.001). SUV_mean and SUV_max measured on PET/MR were significantly lower than on PET/CT for malignant tumours, metastatic neck nodes, benign lesions, bone marrow, and liver (p?<?0.05). The main factor affecting the difference between SUVs in malignant lesions was tumour size (p?<?0.01).

Conclusion

In patients with head and neck tumours, PET/MR showed equivalent performance to PET/CT in terms of qualitative results. Comparison of SUVs revealed an excellent correlation for measurements on both modalities, but underestimation of SUVs measured on PET/MR as compared to PET/CT.     

Role of 18F-FDG PET/CT in the prediction of gastric cancer recurrence after curative surgical resection

Purpose

The study evaluated the role of preoperative ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in the prediction of recurrent gastric cancer after curative surgical resection.

Methods

A total of 271 patients with gastric cancer who underwent ¹⁸F-FDG PET/CT and subsequent curative surgical resection were enrolled. All patients underwent follow-up for cancer recurrence with a mean duration of 24?±?12?months. ¹⁸F-FDG PET/CT images were visually assessed and, in patients with positive ¹⁸F-FDG cancer uptake, the maximum standardized uptake value (SUV_max) of cancer lesions was measured. ¹⁸F-FDG PET/CT findings were tested as prognostic factors for cancer recurrence and compared with conventional prognostic factors. Furthermore, ¹⁸F-FDG PET/CT findings were assessed as prognostic factors according to histopathological subtypes.

Results

Of 271 patients, 47 (17?%) had a recurrent event. Positive ¹⁸F-FDG cancer uptake was shown in 149 patients (55?%). Tumour size, depth of invasion, presence of lymph node metastasis, positive ¹⁸F-FDG uptake and SUV_max were significantly associated with tumour recurrence in univariate analysis, while only depth of invasion, positive ¹⁸F-FDG uptake and SUV_max had significance in multivariate analysis. The 24-month recurrence-free survival rate was significantly higher in patients with negative ¹⁸F-FDG uptake (95?%) than in those with positive ¹⁸F-FDG uptake (74?%; p?18F-FDG uptake was a significant prognostic factor in patients with tubular adenocarcinoma (p?=?0.003) or poorly differentiated adenocarcinoma (p?=?0.0001). However, only marginal significance was shown in patients with signet-ring cell carcinoma and mucinous carcinoma (p?=?0.05).

Conclusion

¹⁸F-FDG uptake of gastric cancer is an independent and significant prognostic factor for tumour recurrence. ¹⁸F-FDG PET/CT could provide effective information on the prognosis after surgical resection of gastric cancer, especially in tubular adenocarcinoma and poorly differentiated adenocarcinoma.     

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.     

Clinical significance of MRI/18F-FDG PET fusion imaging of the spinal cord in patients with cervical compressive myelopathy

Purpose

¹⁸F-FDG PET is used to investigate the metabolic activity of neural tissue. MRI is used to visualize morphological changes, but the relationship between intramedullary signal changes and clinical outcome remains controversial. The present study was designed to evaluate the use of 3-D MRI/¹⁸F-FDG PET fusion imaging for defining intramedullary signal changes on MRI scans and local glucose metabolic rate measured on ¹⁸F-FDG PET scans in relation to clinical outcome and prognosis.

Methods

We studied 24 patients undergoing decompressive surgery for cervical compressive myelopathy. All patients underwent 3-D MRI and ¹⁸F-FDG PET before surgery. Quantitative analysis of intramedullary signal changes on MRI scans included calculation of the signal intensity ratio (SIR) as the ratio between the increased lesional signal intensity and the signal intensity at the level of the C7/T1 disc. Using an Advantage workstation, the same slices of cervical 3-D MRI and ¹⁸F-FDG PET images were fused. On the fused images, the maximal count of the lesion was adopted as the standardized uptake value (SUV_max). In a similar manner to SIR, the SUV ratio (SUVR) was also calculated. Neurological assessment was conducted using the Japanese Orthopedic Association (JOA) scoring system for cervical myelopathy.

Results

The SIR on T1-weighted (T1-W) images, but not SIR on T2-W images, was significantly correlated with preoperative JOA score and postoperative neurological improvement. Lesion SUV_max was significantly correlated with SIR on T1-W images, but not with SIR on T2-W images, and also with postoperative neurological outcome. The SUVR correlated better than SIR on T1-W images and lesion SUV_max with neurological improvement. Longer symptom duration was correlated negatively with SIR on T1-W images, positively with SIR on T2-W images, and negatively with SUV_max.

Conclusion

Our results suggest that low-intensity signal on T1-W images, but not on T2-W images, is correlated with a poor postoperative neurological outcome. SUV_max of lesions showing increased signal intensity and SUVR measured on fusion MRI/PET scans are more sensitive parameters for predicting clinical outcome than signal intensity on the MRI scan.     

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

Purpose

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

Methods

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

Results

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

Conclusion

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

11C-Acetate as a new biomarker for PET/CT in patients with multiple myeloma: initial staging and postinduction response assessment

Purpose

We investigated the potential value of ¹¹C-acetate (ACT) PET/CT in characterizing multiple myeloma (MM) compared with ¹⁸F-FDG PET/CT. Bone marrow histological and whole-body (WB) MRI findings served as the reference standards.

Methods

In this prospective study, 15 untreated MM patients (10 men and 5 women, age range 48?69 years) underwent dual-tracer ¹¹C-ACT and ¹⁸F-FDG PET/CT and WB MRI for pretreatment staging, and 13 of them had repeated examinations after induction therapy. Diffuse and focal bone marrow uptake was assessed by visual and quantitative analyses, including measurement of the maximum standardized uptake value (SUV_max). Between-group differences and correlations were assessed with the Mann-Whitney U test and the Pearson test.

Results

At staging, all 15 patients had diffuse myeloma involvement upon bone marrow examination with 30–90 % of plasma cell infiltrates. Diffuse infiltration was detected in all of them (100 %) using ¹¹C-ACT with a positive correlation between bone marrow uptake values and percentages of plasma cell infiltrates (r = +0.63, p?=?0.01). In contrast, a diagnosis of diffuse infiltration could be established using ¹⁸F-FDG in only six patients (40 %). Focal lesions were shown in 13 patients on both ¹¹C-ACT PET/CT and WB MRI, and in 10 patients on ¹⁸F-FDG PET/CT. Focal lesions demonstrated ¹¹C-ACT uptake with a mean SUV_max of 11.4 ± 3.3 (range 4.6?19.6, n?=?59), which was significantly higher than the ¹⁸F-FDG uptake (mean SUV_max 6.6 ± 3.1, range 2.3?13.7, n?=?29; p?<?0.0001). After treatment, the diffuse bone marrow ¹¹C-ACT uptake showed a mean SUV_max reduction of 66 % in patients with at least a very good partial response versus 34 % in those with at most a partial response only (p?=?0.01).

Conclusion

PET/CT using ¹¹C-ACT as a biomarker showed a higher detection rate for both diffuse and focal myeloma lesions at diagnosis than using ¹⁸F-FDG, and may be valuable for response assessment.     

Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy

Purpose

The aim of this study was to evaluate the association of primary tumour ¹⁸F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake.

Methods

PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUV_max). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses.

Results

In 203 tumours (95?%) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUV_max was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUV_max.

Conclusion

Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT.     

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.     

A new method for apparent diffusion coefficient measurement using sequential 18F-FDG PET and MRI: correlation with histological grade of invasive ductal carcinoma of the breast

Objective

The aim of this study was to measure the apparent diffusion coefficient (ADC) value at the region with the highest FDG uptake using sequential ¹⁸F-FDG PET and MRI, and to correlate it with the histological grade of invasive ductal carcinoma (IDC) of the breast.

Methods

A retrospective study was conducted on 75 untreated patients with IDC. First, a PET/CT scan and subsequent breast MRI were done and the SUV_max of the each breast tumor was recorded. Then, a PET image and ADC map were co-registered. On the axial slice containing the pixel with SUV_max, we drew multiple circular ROIs within the tumor and measured the mean ADC value of each ROI. The average (ADC-mean) and minimum (ADC-min) of the mean ADC values for all ROIs within the tumor were calculated, respectively. Then, a circular ROI was placed at the corresponding location to the pixel with the highest SUV and the mean ADC value of the ROI was denoted as ADC-PET. We compared the averages of the ADC parameters and assessed the correlations among SUV_max and ADC parameters. ROC curve and logistic regression analyses were performed to assess the utility of ADC and SUV_max for detecting histological grade 3.

Results

ADC-min was significantly lower than the ADC-mean or ADC-PET. All of the ADC parameters showed a negative correlation with SUV_max. The area under the ROC curve for identifying histological grade 3 using ADC-PET, ADC-min, ADC-mean and SUV_max was 0.684, 0.660, 0.633 and 0.639, respectively. By multivariate analysis, ADC-PET was a significant, independent predictor of histological grade 3 (p = 0.004).

Conclusions

We estimated the ADC value at the breast tumor region with the highest FDG uptake using sequential ¹⁸F-FDG PET and MRI. This new ADC parameter distinguished high-grade IDC, supporting the feasibility of the combined PET-MRI system in patients with breast cancer.     

<Superscript>18</Superscript>F-FDG and <Superscript>18</Superscript>F-FLT PET/CT imaging in the characterization of mediastinal lymph nodes

Purpose

There is currently no single modality for accurate characterization of enlarged mediastinal lymph nodes into benign or malignant. Recently ¹⁸F-fluorothymidine (FLT) has been used as a proliferation marker. In this prospective study, we examined the role of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) and ¹⁸F-FLT PET/CT in categorizing mediastinal lymph nodes as benign or malignant.

Materials and methods

A total of 70 consecutive patients with mediastinal lymphadenopathy detected on computed tomography (CT) or chest radiograph underwent whole body ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT (within 1 week of each other). Lymph nodal tracer uptake was determined by calculation of standardized uptake value (SUV) with both the tracers. Results of PET/CT were compared with histopathology of the lymph nodes.

Results

Histopathology results showed thirty-seven patients with sarcoidosis, seven patients with tuberculosis, nine patients with non-small cell lung cancer, five patients with Hodgkin’s lymphoma and twelve patients with non-Hodgkin’s lymphoma. The mean FDG SUV_max of sarcoidosis, tuberculosis, Hodgkin’s and non-Hodgkin’s lymphoma was 12.7, 13.4, 8.2, and 8.8, respectively, and the mean FLT SUV_max was 6.0, 5.4, 4.4, and 3.8, respectively. It was not possible to characterize mediastinal lymphadenopathy as benign or malignant solely based on FDG SUV_max values (p > 0.05) or FLT SUV_max values (p > 0.05). There was no significant difference in FDG uptake (p > 0.9) or FLT uptake (p > 0.9) between sarcoidosis and tuberculosis. In lung cancer patients, the FDG SUV_max and FLT SUV_max of those lymph nodes with tumor infiltration on biopsy was 6.7 and 3.9, respectively, and those without nodal infiltration was 6.4 and 3.7, respectively, and both the tracers were not able to characterize the nodal status as malignant or benign (p > 0.05).

Conclusion

Though ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT reflect different aspects of biology, i.e., proliferation and metabolism, respectively, neither tracer could provide satisfactory categorization of benign and malignant lymph nodes. The results of this study clearly suggest that differentiation of mediastinal nodes into benign and malignant solely based on SUV_max values cannot be relied upon, especially in settings where tuberculosis and sarcoidosis are common.

     

Factors affecting intrapatient liver and mediastinal blood pool 18F-FDG standardized uptake value changes during ABVD chemotherapy in Hodgkin’s lymphoma

Purpose

The aim of our study was to assess the intrapatient variability of 2-deoxy-2-(¹⁸F)-fluoro-D-glucose (¹⁸F-FDG) uptake in the liver and in the mediastinum among patients with Hodgkin’s lymphoma (HL) treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy (CHT).

Methods

The study included 68 patients (30 men, 38 women; mean age 32?±?11 years) with biopsy-proven HL. According to Ann Arbor criteria, 6 were stage I, 34 were stage II, 12 were stage 3 and 16 were stage 4. All of them underwent a baseline (PET0) and an interim (PET2) ¹⁸F-FDG whole-body positron emission tomography (PET)/CT. All patients were treated after PET0 with two ABVD cycles for 2 months that ended 15?±?5 days prior to the PET2 examination. All patients were further evaluated 15?±?6 days after four additional ABVD cycles (PET6). None of the patients presented a serum glucose level higher than 107 mg/dl. The mean and maximum standardized uptake values (SUV) of the liver and mediastinum were calculated using the same standard protocol for PET0, PET2 and PET6, respectively. Data were examined by means of the Wilcoxon matched pairs test and linear regression analysis.

Results

The main results of our study were an increased liver SUV_mean in PET2 (1.76?±?0.35) as compared with that of PET0 (1.57?±?0.31; p?<?0.0001) and PET6 (1.69?±?0.28; p?=?0.0407). The same results were obtained when considering liver SUV_max in PET2 (3.13?±?0.67) as compared with that of PET0 (2.82?±?0.64; p?<?0.0001) and PET6 (2.96?±?0.52; p?=?0.0105). No significant differences were obtained when comparing mediastinum SUV_mean and SUV_max in PET0, PET2 and PET6 (p?>?0.05). Another finding is a relationship in PET0 between liver SUV_mean and SUV_max with the stage, which was lower in those patients with advanced disease (r ²?=?0.1456 and p?=?0.0013 for SUV_mean and r ²?=?0.1277 and p?=?0.0028 for SUV_max).

Conclusion

The results of our study suggest that liver ¹⁸F-FDG uptake is variable in patients with HL during the CHT treatment and the disease course and should be considered carefully when used to define the response to therapy in the interim PET in HL.     

Prospective evaluation of solitary thyroid nodule on 18F-FDG PET/CT and high-resolution ultrasonography

Purpose

The utility of 18F-FDG PET/CT in the assessment of thyroid nodules is unclear as there are several conflicting reports on the usefulness of SUV as an indicator to distinguish benign from malignant thyroid lesions. This study incorporated an additional parameter, namely dual time point imaging, to determine the diagnostic accuracy of PET/CT imaging. The performance of 18F-FDG PET/CT was compared to that of high-resolution ultrasound which is routinely used for the evaluation of thyroid nodules.

Methods

Two hundred patients with incidentally detected solitary thyroid nodules were included in the study. Each patient underwent ultrasound and PET/CT evaluation within 7 days of each other, reported by an experienced radiologist and nuclear medicine specialist, respectively, in a blinded manner. The PET/CT criteria employed were maximum SUV (SUV_max) at 60 min and change in SUV_max at delayed (120 min) imaging. Final diagnosis was based on pathological evaluation and follow-up.

Results

Of the 200 patients, 26 had malignant and 174 had benign nodules. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of ultrasound were 80.8, 81.6, 39.6, 96.6 and 81.5%, respectively. Using SUV_max at 60 min as the diagnostic criterion, the above indices were 80.8, 84.5, 43.8, 96.7 and 84%, respectively, for PET/CT. The SUV_max of malignant thyroid lesions was significantly higher than benign lesions (16.2 ± 10.6 vs. 4.5 ± 3.1, respectively; p = 0.0001). Incorporation of percentage change in SUV_max at delayed imaging as the diagnostic criterion yielded a slightly improved sensitivity, specificity, PPV, NPV and accuracy of 84.6, 85.6, 46.8, 97.4 and 85.5%, respectively. There was a significant difference in percentage change in SUV_max between malignant and benign thyroid lesions (14.9 ± 11.4 vs. ?1.6 ± 13.7, respectively; p = 0.0001). However, there was no statistically significant difference (95% confidence interval) between the diagnostic performance of PET/CT and ultrasound.

Conclusions

Routine use of 18F-FDG PET/CT with SUV_max at 60 min as the sole diagnostic criterion does not appear to have a significant advantage over high-resolution ultrasound in the evaluation of thyroid nodules. Incorporation of dual time point imaging enhances image interpretation, and yields a higher diagnostic performance, yet it is not statistically significant. Bearing in mind the cost, limited availability and radiation exposure, routine use of 18F-FDG PET/CT for distinguishing benign from malignant thyroid nodules cannot be recommended.     

Differentiating the grades of thymic epithelial tumor malignancy using textural features of intratumoral heterogeneity via <Superscript>18</Superscript>F-FDG PET/CT

Objective

We aimed to explore the ability of textural heterogeneity indices determined by ¹⁸F-FDG PET/CT for grading the malignancy of thymic epithelial tumors (TETs).

Methods

We retrospectively enrolled 47 patients with pathologically proven TETs who underwent pre-treatment ¹⁸F-FDG PET/CT. TETs were classified by pathological results into three subgroups with increasing grades of malignancy: low-risk thymoma (LRT; WHO classification A, AB and B1), high-risk thymoma (B2 and B3), and thymic carcinoma (TC). Using ¹⁸F-FDG PET/CT, we obtained conventional imaging indices including SUV_max and 20 intratumoral heterogeneity indices: i.e., four local-scale indices derived from the neighborhood gray-tone difference matrix (NGTDM), eight regional-scale indices from the gray-level run-length matrix (GLRLM), and eight regional-scale indices from the gray-level size zone matrix (GLSZM). Area under the receiver operating characteristic curve (AUC) was used to demonstrate the abilities of the imaging indices for differentiating subgroups. Multivariable logistic regression analysis was performed to show the independent significance of the textural indices. Combined criteria using optimal cutoff values of the SUV_max and a best-performing heterogeneity index were applied to investigate whether they improved differentiation between the subgroups.

Results

Most of the GLRLM and GLSZM indices and the SUV_max showed good or fair discrimination (AUC >0.7) with best performance for some of the GLRLM indices and the SUV_max, whereas the NGTDM indices showed relatively inferior performance. The discriminative ability of some of the GLSZM indices was independent from that of SUV_max in multivariate analysis. Combined use of the SUV_max and a GLSZM index improved positive predictive values for LRT and TC.

Conclusions

Texture analysis of ¹⁸F-FDG PET/CT scans has the potential to differentiate between TET tumor grades; regional-scale indices from GLRLM and GLSZM perform better than local-scale indices from the NGTDM. The SUV_max and heterogeneity indices may have complementary value in differentiating TET subgroups.

     

Characterisation of malignant peripheral nerve sheath tumours in neurofibromatosis-1 using heterogeneity analysis of <Superscript>18</Superscript>F-FDG PET

Purpose

Measurement of heterogeneity in ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) images is reported to improve tumour phenotyping and response assessment in a number of cancers. We aimed to determine whether measurements of ¹⁸F-FDG heterogeneity could improve differentiation of benign symptomatic neurofibromas from malignant peripheral nerve sheath tumours (MPNSTs).

Methods

¹⁸F-FDG PET data from a cohort of 54 patients (24 female, 30 male, mean age 35.1 years) with neurofibromatosis-1 (NF1), and clinically suspected malignant transformation of neurofibromas into MPNSTs, were included. Scans were performed to a standard clinical protocol at 1.5 and 4 h post-injection. Six first-order [including three standardised uptake value (SUV) parameters], four second-order (derived from grey-level co-occurrence matrices) and four high-order (derived from neighbourhood grey-tone difference matrices) statistical features were calculated from tumour volumes of interest. Each patient had histological verification or at least 5 years clinical follow-up as the reference standard with regards to the characterisation of tumours as benign (n = 30) or malignant (n = 24).

Results

There was a significant difference between benign and malignant tumours for all six first-order parameters (at 1.5 and 4 h; p < 0.0001), for second-order entropy (only at 4 h) and for all high-order features (at 1.5 h and 4 h, except contrast at 4 h; p < 0.0001–0.047). Similarly, the area under the receiver operating characteristic curves was high (0.669–0.997, p < 0.05) for the same features as well as 1.5-h second-order entropy. No first-, second- or high-order feature performed better than maximum SUV (SUVmax) at differentiating benign from malignant tumours.

Conclusions

¹⁸F-FDG uptake in MPNSTs is higher than benign symptomatic neurofibromas, as defined by SUV parameters, and more heterogeneous, as defined by first- and high-order heterogeneity parameters. However, heterogeneity analysis does not improve on SUVmax discriminative performance.

     

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.