Preoperative PET/CT FDG standardized uptake value of pelvic lymph nodes as a significant prognostic factor in patients with uterine cervical cancer

Purpose

Using integrated PET/CT, we evaluated the prognostic relevance in uterine cervical cancer of preoperative pelvic lymph node (LN) [¹⁸F]FDG uptake.

Methods

Patients with FIGO stage IB to IIA uterine cervical cancer were imaged with FDG PET/CT before radical surgery. We used Cox proportional hazards regression to examine the relationship between recurrence and the FDG maximum standardized uptake value (SUV_max) in the pelvic LN (SUV_LN) on PET/CT.

Results

Clinical data, treatment modalities, and results in 130 eligible patients were reviewed. The median postsurgical follow-up was 34 months (range 6 to 109 months). Receiver operating characteristic analysis identified SUV_LN 2.36 as the most significant cut-off value for predicting recurrence. SUV_LN was correlated with SUV_tumour (P?=?0.002), primary tumour size (P?=?0.004), and parametrial invasion (P?=?0.013). Univariate analyses showed significant associations between recurrence and SUV_LN (P?=?0.001), SUV_tumour (P?=?0.007), pelvic LN metastasis (P?=?0.002), parametrial invasion (P?<?0.001), primary tumour size (P?=?0.007), suspected LN metastasis on MRI (P?=?0.024), and FIGO stage (P?=?0.026). Multivariate analysis identified SUV_LN (P?=?0.013, hazard ratio, HR, 4.447, 95 % confidence interval, CI, 1.379 – 14.343) and parametrial invasion (P?=?0.013, HR 6.728, 95 % CI 1.497 – 30.235) as independent risk factors for recurrence. Patients with SUV_LN ≥2.36 and SUV_LN <2.36 differed significantly in terms of recurrence (HR 15.20, P?<?0.001).

Conclusion

Preoperative pelvic LN FDG uptake showed a strong significant association with uterine cervical cancer recurrence.     

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.

     

Preoperative lymph node staging in patients with primary prostate cancer: comparison and correlation of quantitative imaging parameters in diffusion-weighted imaging and 11C-choline PET/CT

Purpose

To compare the diagnostic performance of DWI and 11C-choline PET/CT in the assessment of preoperative lymph node status in patients with primary prostate cancer.

Material and methods

Thirty-three patients underwent DWI and 11C-choline PET/CT prior to prostatectomy and extended pelvic lymph node dissection. Mean standardised uptake value (SUV_mean) and mean apparent diffusion coefficient (ADC) of 76 identified lymph nodes (LN) were measured and correlated with histopathology. ADC values and SUVs were compared using linear regression analysis.

Results

A significant difference between benign and malignant LN was observed for ADC values (1.17 vs. 0.96?×?10^-3 mm²/s; P?<?0.001) and SUV_mean (1.61 vs. 3.20; P?<?0.001). ROC analysis revealed an optimal ADC threshold of 1.01?×?10^-3 mm²/s for differentiating benign from malignant LN with corresponding sensitivity/specificity of 69.70 %/78.57 % and an area under the curve (AUC) of 0.785. The optimal threshold for SUV_mean was 2.5 with corresponding sensitivity/specificity of 69.72 %/90.48 % and with an AUC of 0.832. ADC values and SUV_mean showed a moderate significant inverse correlation (r?=?-0.63).

Conclusion

Both modalities reveal similar moderate diagnostic performance for preoperative lymph node staging of prostate cancer, not justifying their application in routine clinical practice at this time. The only moderate inverse correlation between ADC values and SUV_mean suggests that both imaging parameters might provide complementary information on tumour biology.

Key Points

? Conventional imaging shows low performance for lymph node staging in prostate cancer. ? DWI and 11C-choline PET/CT both provide additional functional information ? Both functional modalities reveal only moderate diagnostic performance.     

Dual-time-point F-18 FDG PET/CT for evaluation in patients with malignant lymphoma

Objective

The aim of this study was to evaluate the usefulness of F-18 fluorodeoxyglucose (FDG) dual-time-point (DTP) positron emission tomography (PET)/computed tomography (CT) with semiquantitative analyses for the initial staging in patients with malignant lymphoma.

Methods

Forty-three patients had DTP PET/CT, with 60-min and 2-h scan [n?=?8, Hodgkin??s lymphoma (HL); n?=?12, indolent non-Hodgkin lymphoma (NHL); n?=?23, aggressive NHL].

Results

A total of 524 lesions were evaluated (406 lymph nodes and 118 extra-nodal lesions). The maximum standardized uptake value (SUV_max) on 2-h delayed scan (SUV₂) was significantly higher than those on 1-h early scan (SUV₁) for all groups (P?<?0.0001 for HL; P?<?0.0001 for indolent NHL; P?<?0.0001 for aggressive NHL). Significant differences were detected between HL and indolent NHL, between indolent NHL and the aggressive NHL for both SUV₁ and SUV₂ (each P?<?0.0001). No significant differences were detected between HL and aggressive NHL for both SUV₁ and SUV₂ (P?=?0.6891 for SUV₁; P?=?0.8828 for SUV₂); however, significant differences were detected for the retention index of SUV_max between these groups (P?=?0.0238).

Conclusions

DTP F-18 FDG PET/CT with a semiquantitative technique may have the potential to provide the more accurate diagnoses for the staging of malignant lymphoma and the more important role in predicting the histological grades of malignancy compared with single-time-point F-18 FDG-PET scan.     

Prognostic importance of lymph node-to-primary tumor standardized uptake value ratio in invasive squamous cell carcinoma of uterine cervix

Purpose

Using integrated PET/CT, we evaluated the prognostic value of [¹⁸F]FDG uptake ratio between pelvic lymph node (LN) and primary tumor in invasive squamous cell carcinoma (SCCA) of the uterine cervix.

Methods

We retrospectively reviewed patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB to IIA cervical SCCA who underwent preoperative [¹⁸F]FDG PET/CT scans. PET/CT parameters such as maximum standardized uptake value (SUV) of the primary cervical cancer (SUV_cervix) and LN (SUV_LN), and the LN-to-cervical cancer SUV ratio (SUV_LN/SUV_cervix) were assessed. Prognostic values of PET/CT-derived metabolic and volumetric variables and clinicopathology parameters were analyzed to predict progression-free survival (PFS) in regression analyses.

Results

Clinical data, treatment modalities, and results were reviewed for 103 eligible patients. Median post-surgical follow-up was 29 months (range, 6–89), and 19 (18.5%) patients experienced recurrence. Multivariate logistic regression analysis showed that SUV_LN / SUV_cervix > 0.1747(P = 0.048) was the independent risk factor of recurrence. Patient group categorized by SUV_LN/SUV_cervix showed significant difference in PFS (log-rank test, P < 0.001).

Conclusions

Preoperative SUV_LN/SUV_cervix measured by [¹⁸F]FDG PET/CT was significantly associated with recurrence, and has an incremental prognostic value for PFS in patients with cervical SCCA.

     

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

Purpose

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

Methods

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

Results

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

Conclusion

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

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.     

Correlation of breast cancer subtypes,based on estrogen receptor,progesterone receptor,and HER2, with functional imaging parameters from 68Ga-RGD PET/CT and 18F-FDG PET/CT

Purpose

Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes.

Methods

In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6?±?7.5 years old). ⁶⁸Ga-Labeled arginine-glycine-aspartic acid (RGD) and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUV_max and SUV_avg) from RGD PET/CT and SUV_max and SUV_avg from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2?, ER/PR+,Her2+, ER/PR?,Her2+, and ER/PR?,Her2?), were considered.

Results

Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88?±?8.73 vs 10.48?±?6.01, p?=?0.02 for SUV_max; 9.40?±?5.19 vs 5.92?±?4.09, p?=?0.02 for SUV_avg) and the PR-negative group (8.37?±?4.94 vs 4.79?±?3.93, p?=?0.03 for SUV_avg). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42?±?0.59 vs 2.90?±?0.75, p?=?0.04 for SUV_max; 1.60?±?0.38 vs 1.95?±?0.53, p?=?0.04 for SUV_avg) and showed a significant positive correlation with the HER2/CEP17 ratio (r?=?0.38, p?=?0.03 for SUV_max and r?=?0.46, p?<?0.01 for SUV_avg). FDG PET parameters showed significantly higher values in the ER/PR?,Her2? subgroup versus the ER/PR+,Her2? or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER/PR?,Her2? subgroup versus the other subgroups. There was no correlation between FDG and RGD PET parameters in the overall group. Only the ER/PR?,Her2? subgroup showed a significant positive correlation between FDG and RGD PET parameters (r?=?0.59, p?=?0.03 for SUV_max).

Conclusion

⁶⁸Ga-RGD and ¹⁸F-FDG PET/CT are promising functional imaging modalities for predicting biomarkers and molecular phenotypes in breast cancer patients.     

Morphological, functional and metabolic imaging biomarkers: assessment of vascular-disrupting effect on rodent liver tumours

Objectives

To evaluate effects of a vascular-disrupting agent on rodent tumour models.

Methods

Twenty rats with liver rhabdomyosarcomas received ZD6126 intravenously at 20 mg/kg, and 10 vehicle-treated rats were used as controls. Multiple sequences, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) with the microvascular permeability constant (K), were acquired at baseline, 1 h, 24 h and 48 h post-treatment by using 1.5-T MRI. [¹⁸F]fluorodeoxyglucose micro-positron emission tomography (¹⁸F-FDG µPET) was acquired pre- and post-treatment. The imaging biomarkers including tumour volume, enhancement ratio, necrosis ratio, apparent diffusion coefficient (ADC) and K from MRI, and maximal standardised uptake value (SUV_max) from FDG µPET were quantified and correlated with postmortem microangiography and histopathology.

Results

In the ZD6126-treated group, tumours grew slower with higher necrosis ratio at 48 h (P?<?0.05), corresponding well to histopathology; tumour K decreased from 1 h until 24 h, and partially recovered at 48 h (P?<?0.05), parallel to the evolving enhancement ratios (P?<?0.05); ADCs varied with tumour viability and perfusion; and SUV_max dropped at 24 h (P?<?0.01). Relative K of tumour versus liver at 48 h correlated with relative vascular density on microangiography (r?=?0.93, P?<?0.05).

Conclusions

The imaging biomarkers allowed morphological, functional and metabolic quantifications of vascular shutdown, necrosis formation and tumour relapse shortly after treatment. A single dose of ZD6126 significantly diminished tumour blood supply and growth until 48 h post-treatment.     

Assessment of the metabolic flow phenotype of primary colorectal cancer: correlations with microvessel density are influenced by the histological scoring method

Objectives

To investigate how the histological scoring of microvessel density affects correlations between integrated ¹⁸F-FDG-PET/perfusion CT parameters and CD105 microvessel density.

Methods

A total of 53 patients were enrolled from 2007 to 2010. Integrated ¹⁸F-FDG-PET/perfusion CT was successful in 45 patients, 35 of whom underwent surgery without intervening treatment. Tumour SUV_max, SUV_mean and regional blood flow (BF) were derived. Immunohistochemical staining for CD105 expression and analysis were performed for two hot spots, four hot spots and the Chalkley method. Correlations between metabolic flow parameters and CD105 expression were assessed using Spearman’s rank correlation.

Results

Mean (SD) for tumour size was 38.5 (20.5)?mm, for SUV_max, SUV_mean and BF it was 19.1 (4.5), 11.6 (2.5) and 85.4 (40.3)?mL/min/100?g tissue, and for CD105 microvessel density it was 71.4 (23.6), 66.8 (22.9) and 6.18 (2.07) for two hot spots, four hot spots and the Chalkley method, respectively. Positive correlation between BF and CD105 expression was modest but higher for Chalkley than for four hot spots analysis (r?=?0.38, P?=?0.03; r?=?0.33, P?=?0.05, respectively). There were no significant correlations between metabolic parameters (SUV_max or SUV_mean) and CD105 expression (r?=?0.08–0.22, P?=?0.21–0.63).

Conclusions

The histological analysis method affects correlations between tumour CD105 expression and BF but not SUV_max or SUV_mean.

Key Points

? FDG-PET/perfusion CT offers new surrogate biomarkers of angiogenesis. ? Microvessel density scoring influences histopathological correlations with CT blood flow. ? Highest correlations were found with the Chalkley analysis method. ? Correlations between SUV and CD105 are not affected by the scoring method.     

Tumor hypoxia and microscopic diffusion capacity in brain tumors: A comparison of 62Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) PET/CT and diffusion-weighted MR imaging

Objectives

The aim of this study was to clarify the relationship between tumor hypoxia and microscopic diffusion capacity in primary brain tumors using ⁶²Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) (⁶²Cu-ATSM) PET/CT and diffusion-weighted MR imaging (DWI).

Methods

This study was approved by the institutional human research committee and was HIPAA compliant, and informed consent was obtained from all patients. ⁶²Cu-ATSM PET/CT and DWI were performed in a total of 40 primary brain tumors of 34 patients with low grade glioma (LGG, n?=?13), glioblastoma (GBM, n?=?20), and primary central nervous system lymphoma (PCNSL, n?=?7). ⁶²Cu-ATSM PET/CT parameters and apparent diffusion coefficient (ADC) obtained by DWI were compared.

Results

High intensity signals by ⁶²Cu-ATSM PET/CT and DWI in patients with GBM and PCNSL, and low intensity signals in LGG patients were observed. An inverse correlation was found between maximum SUV (SUV_max) and minimum ADC (ADC_min) (r?=??0.583, p?<?0.0001), and between tumor/brain ratio (T/B_ratio) and ADC_min for all tumors (r?=??0.532, p?<?0.0001). Both SUV_max and T/B_ratio in GBM were higher than LGG (p?<?0.0001 and p?<?0.0001), and those in PCNSL were also higher than GBM (p?=?0.033 and p?=?0.044). The ADC_min was lower in GBM (p?=?0.011) and PCNSL (p?=?0.01) than in LGG, while no significant difference was found between GBM and PCNSL (p?=?0.90).

Conclusion

Tumor hypoxia assessed by ⁶²Cu-ATSM PET/CT correlated with microscopic diffusion capacity obtained by DWI in brain tumors. Both ⁶²Cu-ATSM PET/CT and DWI were considered feasible imaging methods for grading glioma. However, ⁶²Cu-ATSM PET/CT provided additional diagnostic information to differentiate between GBM and PCNSL.     

PET/CT studies of multiple myeloma using 18 F-FDG and 18 F-NaF: comparison of distribution patterns and tracers’ pharmacokinetics

Objective

The aim of this prospective study is to evaluate the combined use of fluorine-18 fluorodeoxyglucose (¹⁸?F-FDG) and fluorine-18 sodium fluoride (¹⁸?F-NaF) PET/CT in the skeletal assessment of patients with multiple myeloma (MM) and to compare the efficacy of these two PET tracers regarding detection of myeloma-indicative osseous lesions.

Patients and methods

The study includes 60 patients with multiple myeloma (MM) diagnosed according to standard criteria. All patients underwent dynamic (dPET/CT) scanning of the pelvis as well as whole body PET/CT studies with both tracers. The interval between the two exams was one day. Sites of focal increased ¹⁸?F-FDG uptake were considered as highly suspicious of myelomatous involvement. The lesions detected on the ¹⁸?F-NaF PET/CT scans were then correlated with those detected on ¹⁸?F-FDG PET/CT, which served as a reference. Moreover, the ¹⁸?F-FDG PET/CT results were also correlated with the low-dose CT findings. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a 2-tissue compartment model and a non-compartmental approach.

Results

Whole body ¹⁸?F-FDG PET/CT revealed approximately 343 focal lesions while ¹⁸?F-NaF PET/CT revealed 135 MM-indicative lesions (39 % correlation). CT demonstrated 150 lesions that correlated with those in ¹⁸?F-FDG PET/CT (44 % correlation). Six patients demonstrated a diffuse pattern of disease with ¹⁸?F-FDG, while 15 of them had a mixed (diffuse and focal) pattern of skeletal ¹⁸?F-FDG uptake. A high number of degenerative, traumatic and arthritic disease lesions were detected with ¹⁸?F-NaF PET/CT. In three patients with multiple focal ¹⁸?F-FDG-uptake, ¹⁸?F-NaF PET/CT failed to demonstrate any bone lesion. The dPET/CT scanning of the pelvic area with ¹⁸?F-FDG and ¹⁸?F-NaF revealed 77 and 24 MM-indicative lesions, respectively. Kinetic analysis of ¹⁸?F-FDG revealed the following mean values: SUV_aver?=?5.1, k₁?=?0.37 (1/min), k₃?=?0.10 (1/min), V_B?=?0.06, influx?=?0.04 (1/min), FD?=?1.28; the respective values for ¹⁸?F-NaF were SUV_average?=?10.7, k₁?=?0.25 (1/min), k₃?=?0.34 (1/min), V_B?=?0.02, influx?=?0.10 (1/min), FD?=?1.37. Apart from the correlation between V_B of ¹⁸?F-FDG and k₁ of ¹⁸?F-NaF (r?=?0.54), no other significant correlation was observed between the two tracers’ kinetic parameters. We found a significant correlation between FD and SUV_average (r?=?0.93), FD and SUV_max (r?=?0.80), FD and influx ( r?=?0.85), as well as between influx and SUV_average (r?=?0.74) for ¹⁸?F-FDG. In ¹⁸?F-NaF we observed the most significant correlations between FD and SUV_average (r?=?0.97), FD and SUV_max (r?=?0.87), and between influx and k₁ (r?=?0.72).

Conclusion

The combined use of ¹⁸?F-FDG PET/CT and ¹⁸?F-NaF PET/CT provides different molecular information regarding the biological processes that take place in a MM osseous lesion. ¹⁸?F-FDG PET/CT proved to be a more specific biomarker than ¹⁸?F-NaF PET/CT in multiple myeloma skeletal assessment.     

Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer

Purpose

The objective of this study was to assess the prognostic value of metabolic tumor burden on 2-deoxy-2-[¹⁸F]fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET)/CT measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG), independent of Union Internationale Contra la Cancrum (UICC)/American Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) stage, in comparison with that of standardized uptake value (SUV) in nonsurgical patients with non-small cell lung cancer (NSCLC).

Methods

This study retrospectively reviewed 169 consecutive nonsurgical patients (78 men, 91 women, median age of 68?years) with newly diagnosed NSCLC who had pretreatment ¹⁸F-FDG PET/CT scans. The ¹⁸F-FDG PET/CT scans were performed in accordance with National Cancer Institute guidelines. The MTV of whole-body tumor (MTV_WB), of primary tumor (MTV_T), of nodal metastases (MTV_N), and of distant metastases (MTV_M); the TLG of whole-body tumor (TLG_WB), of primary tumor (TLG_T), of nodal metastases (TLG_N), and of distant metastases (TLG_M); the SUV_max of whole-body tumor (SUV_maxWB), of primary tumor (SUV_maxT), of nodal metastases (SUV_maxN), and of distant metastases (SUV_maxM) as well as the SUV_mean of whole-body tumor (SUV_meanWB), of primary tumor (SUV_meanT), of nodal metastases (SUV_meanN), and of distant metastases (SUV_meanM) were measured with the PETedge tool on a MIMvista workstation with manual adjustment. The median follow-up among survivors was 35?months from the PET/CT (range 2?C82?months). Statistical methods included Kaplan-Meier curves, Cox regression, and C-statistics.

Results

There were a total of 139 deaths during follow-up. Median overall survival (OS) was 10.9?months [95% confidence interval (CI) 9.0?C13.2?months]. The MTV was statistically associated with OS. The hazard ratios (HR) for 1 unit increase of ln(MTV_WB), ??(MTV_T), ??(MTV_N), and ??(MTV_M) before/after adjusting for stage were: 1.47/1.43 (p?p?p?p?=?0.007/0.043), respectively. TLG had statistically significant associations with OS with the HRs for 1 unit increase in ln(TLG_WB), ??(TLG_T), ??(TLG_N), and ??(TLG_M) before/after adjusting for stage being 1.36/1.33 (p?p?=?0.001/0.002), 1.05/1.04 (p?p?=?0.003/0.024), respectively. The ln(SUV_maxWB) and ??(SUV_maxN) were statistically associated with OS with the corresponding HRs for a 1 unit increase before/after adjusting for stage being 1.46/1.43 (p?=?0.013/0.024) and 1.22/1.16 (p?=?0.002/0.040). The ??(SUV_meanN) was statistically associated with OS before and after adjusting for stage with HRs for a 1 unit increase of 1.32 (p?p?=?0.015), respectively. The ??(SUV_meanM) and ??(SUV_maxM) were statistically associated with OS before adjusting for stage with HRs for a 1 unit increase of 1.26 (p?=?0.017) and 1.18 (p?=?0.007), respectively, but not after adjusting for stage (p?=?0.127 and 0.056). There was no statistically significant association between OS and ??(SUV_maxT), ln(SUV_meanWB), or ??(SUV_meanT). There was low interobserver variability among three radiologists with intraclass correlation coefficients (ICC) greater than 0.94 for SUV_maxWB, ln(MTV_WB), and ln(TLG_WB). Interobserver variability was higher for SUV_meanWB with an ICC of 0.806.

Conclusion

Baseline metabolic tumor burdens at the level of whole-body tumor, primary tumor, nodal metastasis, and distant metastasis as measured with MTV and TLG on FDG PET are prognostic measures independent of clinical stage with low inter-observer variability and may be used to further stratify nonsurgical patients with NSCLC. This study also suggests MTV and TLG are better prognostic measures than SUV_max and SUV_mean. These results will need to be validated in larger cohorts in a prospective study.     

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.     

Integrated 18F-FDG PET/perfusion CT for the monitoring of neoadjuvant chemoradiotherapy in rectal carcinoma: correlation with histopathology

Purpose

The aim of this study was to prospectively monitor changes in the flow-metabolic phenotype (ΔFMP) of rectal carcinoma (RC) after neoadjuvant chemoradiotherapy (CRT) and to evaluate whether ΔFMP of RC correlate with histopathological prognostic factors including response to CRT.

Methods

Sixteen patients with RC (12 men, mean age 60.7?±?12.8 years) underwent integrated ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/perfusion CT (PET/PCT), followed by neoadjuvant CRT and surgery. In 13 patients, PET/PCT was repeated after CRT. Perfusion [blood flow (BF), blood volume (BV), mean transit time (MTT)] and metabolic [maximum and mean standardized uptake values (SUV_max, SUV_mean)] parameters as well as the FMP (BF × SUV_max) were determined before and after CRT by two independent readers and correlated to histopathological prognostic factors of RC (microvessel density, necrosis index, regression index, vascular invasion) derived from resected specimens. The diagnostic performance of ΔFMP for prediction of treatment response was determined.

Results

FMP significantly decreased after CRT (p?<?0.001), exploiting higher changes after CRT as compared to changes of perfusion and metabolic parameters alone. Before CRT, no significant correlations were found between integrated PET/PCT and any of the histopathological parameters (all p?>?0.05). After CRT, BV and SUV_max correlated positively with the necrosis index (r?=?0.67/0.70), SUV_max with the invasion of blood vessels (r?=?0.62) and ΔFMP with the regression index (r?=?0.88; all p?<?0.05). ΔFMP showed high accuracy for prediction of histopathological response to CRT (AUC 0.955, 95 % confidence interval 0.833–1.000, p?<?0.01) using a cut-off value of ?75 %.

Conclusion

In RC, ΔFMP derived from integrated ¹⁸F-FDG PET/PCT is useful for monitoring the effects of neoadjuvant CRT and allows prediction of histopathological response to CRT.     

Reevaluation of FDG-PET/CT in patients with hoarseness caused by vocal cord palsy

Objective

Vocal cord palsy (VCP) is a potential cause of hoarseness that results in decreasing mobility of the vocal cord. VCP can arise from a variety of causes; so, systematic screening is warranted for the management of patients with VCP. Asymmetrical fluorodeoxyglucose (FDG) uptake in vocal cords is a well-known feature in patients with VCP, but no detailed analysis has been performed. This study aimed at reevaluating the ¹⁸F-FDG positron emission tomography/computed tomography (PET/CT) for patients with VCP.

Methods

We retrospectively surveyed the results of FDG-PET/CT for 59 patients with VCP, compared to laryngoscopic findings. Quantitative analysis was performed using maximum standardized uptake value (SUV_max), and regions of interest were drawn over bilateral vocal cords as confirmed from the CT portion of PET/CT. Patients were divided into 3 groups: Group 1 (n?=?14), in which VCP was caused by the lesion of the laryngeal area; Group 2 (n?=?40), in which VCP was caused by the lesion on the root of the recurrent laryngeal nerve; and Group 3 (n?=?5), in which VCP was caused by the lesion from the vagal center to the proximal vagus nerve.

Results

For Group 1, higher FDG uptake in the paralyzed vocal cord was seen in 86?% of patients (mean SUV_max 8.1?±?5.3 vs. 2.3?±?0.4, paralyzed vs. non-paralyzed, respectively; P?<?0.002). The sensitivity of FDG-PET/CT for indicating the lesion causing VCP was 79?% for Group 1. Group 2 showed dominant FDG uptake in the non-paralyzed vocal cord (mean SUV_max 2.1?±?0.9 vs. 1.5?±?0.4, non-paralyzed vs. paralyzed, respectively; P?<?0.001). The sensitivity of FDG-PET/CT for indicating the lesion causing VCP was 93?% for Group 2. Group 3 showed no statistically significant difference in FDG accumulation between non-paralyzed and paralyzed vocal cords (mean SUV_max 1.8?±?0.3 vs. 1.7?±?0.3, non- paralyzed vs. paralyzed, respectively; P?=?0.30). The sensitivity of FDG-PET/CT for indicating the lesion causing VCP was 60?% for Group 3.

Conclusions

FDG accumulation in the vocal cords is dependent on the lesion site causing VCP. In addition, FDG-PET/CT can contribute to identification of the lesion responsible for inducing VCP.     

Evaluation of intratumoural heterogeneity on 18F-FDG PET/CT for characterization of peripheral nerve sheath tumours in neurofibromatosis type 1

Purpose

The aim of the study was to evaluate the potential usefulness of intratumoural tracer uptake heterogeneity on ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT as compared to a cut-off maximum standardized uptake value (SUV_max) for characterization of peripheral nerve sheath tumours (PNSTs) in neurofibromatosis type 1 (NF1).

Methods

Fifty patients suffering from NF1 were examined by ¹⁸F-FDG PET/CT. Intralesional tracer uptake was analysed qualitatively and semi-quantitatively by measuring the mean and maximum SUV. Uptake heterogeneity was graded qualitatively using a three-point scale and semi-quantitatively by calculating an SUV-based heterogeneity index (HI_SUV). Cohen’s κ was used to determine inter- and intra-rater agreement. Histopathological evaluation and clinical as well as radiological follow-up examinations served as the reference standards.

Results

A highly significant correlation between the degree of intratumoural uptake heterogeneity on ¹⁸F-FDG PET and malignant transformation of PNSTs was observed (p?<?0.0001). Semi-quantitative HI_SUV was significantly higher in malignant PNSTs (MPNSTs) than in benign tumours (p?=?0.0002). Both intralesional heterogeneity and SUV_max could be used to identify malignant tumours with a sensitivity of 100 %. Cohen’s κ was 0.86 for inter-rater agreement and 0.88 for intra-rater agreement on heterogeneity.

Conclusion

MPNSTs in patients with NF1 demonstrate considerable intratumoural uptake heterogeneity on ¹⁸F-FDG PET/CT. Assessment of tumour heterogeneity is highly reproducible. Both tumour heterogeneity and a cut-off SUV_max may be used to sensitively identify malignant PNSTs, but the specificity is higher for the latter. A combination of both methods leads to a non-significant improvement in diagnostic performance.     

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

Purpose

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

Methods

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

Results

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

Conclusion

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

Combined use of 18F-FDG PET/CT and MRI for response monitoring of breast cancer during neoadjuvant chemotherapy

Purpose

To explore the potential complementary value of PET/CT and dynamic contrast-enhanced MRI in predicting pathological response to neoadjuvant chemotherapy (NAC) of breast cancer and the dependency on breast cancer subtype.

Methods

We performed ¹⁸F-FDG PET/CT and MRI examinations before and during NAC. The imaging features evaluated on both examinations included baseline and changes in ¹⁸F-FDG maximum standardized uptake value (SUVmax) on PET/CT, and tumour morphology and contrast uptake kinetics on MRI. The outcome measure was a (near) pathological complete response ((near-)pCR) after surgery. Receiver operating characteristic curves with area under the curve (AUC) were used to evaluate the relationships between patient, tumour and imaging characteristics and tumour responses.

Results

Of 93 patients, 43 achieved a (near-)pCR. The responses varied among the different breast cancer subtypes. On univariate analysis the following variables were significantly associated with (near-)pCR: age (p?=?0.033), breast cancer subtype (p?<?0.001), relative change in SUVmax on PET/CT (p?<?0.001) and relative change in largest tumour diameter on MRI (p?<?0.001). The AUC for the relative reduction in SUVmax on PET/CT was 0.78 (95 % CI 0.68–0.88), and for the relative reduction in tumour diameter at late enhancement on MRI was 0.79 (95 % CI 0.70–0.89). The AUC increased to 0.90 (95 % CI 0.83–0.96) in the final multivariate model with PET/CT, MRI and breast cancer subtype combined (p?=?0.012).

Conclusion

PET/CT and MRI showed comparable value for monitoring response during NAC. Combined use of PET/CT and MRI had complementary potential. Research with more patients is required to further elucidate the dependency on breast cancer subtype.