Quantitative evaluation of bone metastases from prostate cancer with simultaneous [18F] choline PET/MRI: combined SUV and ADC analysis

Objective

To quantitatively analyze bone metastases from prostate cancer and correlate the apparent diffusion coefficients (ADCs) and standardized uptake values (SUVs).

Methods

Fifty-five patients with biopsy-proven prostate cancer or suspected recurrent prostate cancer were examined with simultaneous [¹⁸F] choline Positron emission tomography (PET)/MRI at 3 T. In 11 patients, thirty-two PET-positive bone lesions could be identified that were located in the field-of-view of the Diffusion weighted imaging-sequence. Region-of-interest and volume-of-interest analyses were performed to measure the mean and minimal ADCs and to assess maximum and mean SUVs of every bone lesion. Correlations between maximum and mean SUVs and mean and minimal ADCs were calculated.

Results

The SUV_max of all lesions was 5.5 ± 3.1 (mean ± SD). The SUV_mean was 1.8 ± 0.9. The mean ADC (ADC_mean) of all lesions was 0.67 ± 0.13 × 10^?3 mm²/s. The minimal ADC (ADC_min) of all lesions was 0.56 ± 0.14 × 10^?3 mm²/s. There was a moderate but significant inverse correlation of SUV_max vs. ADC_mean with a correlation coefficient of ?0.4 (p = 0.02). There was also a significant inverse correlation of SUV_max vs. ADC_min with r = ?0.41 (p = 0.02).

Conclusion

Our initial results demonstrate a moderate but significant inverse correlation between increased choline metabolism and ADC values of bone metastases from prostate cancer. Further research on a multimodality approach using simultaneous PET/MRI in bone metastasis of prostate cancer seems to be justified.     

Diffusion weighted imaging of the normal breast: reproducibility of apparent diffusion coefficient measurements and variation with menstrual cycle and menopausal status

Objectives

To establish the reproducibility of apparent diffusion coefficient (ADC) measurements in normal fibroglandular breast tissue and to assess variation in ADC values with phase of the menstrual cycle and menopausal status.

Methods

Thirty-one volunteers (13 premenopausal, 18 postmenopausal) underwent magnetic resonance twice (interval 11–22?days) using diffusion-weighted MRI. ADC_total and a perfusion-insensitive ADC_high (omitting b?=?0) were calculated. Reproducibility and inter-observer variability of mean ADC values were assessed. The difference in mean ADC values between the two phases of the menstrual cycle and the postmenopausal breast were evaluated.

Results

ADC_total and ADC_high showed good reproducibility (r%?=?17.6, 22.4). ADC_high showed very good inter-observer agreement (kappa?=?0.83). The intraclass correlation coefficients (ICC) were 0.93 and 0.91. Mean ADC values were significantly lower in the postmenopausal breast (ADC_total 1.46?±?0.3?×?10^-3?mm²/s, ADC_high 1.33?±?0.3?×?10^-3?mm²/s) compared with the premenopausal breast (ADC_total 1.84?±?0.26?×?10^-3?mm²/s, ADC_high 1.77?±?0.26?×?10^-3?mm²/s; both P?total P?=?0.2, ADC_high P?=?0.24) or between postmenopausal women taking or not taking oestrogen supplements (ADC_total P?=?0.6, ADC_high P?=?0.46).

Conclusions

ADC values in fibroglandular breast tissue are reproducible. Lower ADC values within the postmenopausal breast may reduce diffusion-weighted contrast and have implications for accurately detecting tumours.

Key Points

? ADC values from fibroglandular breast tissue are measured reproducibly by multiple observers. ? Mean ADC values were significantly lower in postmenopausal than premenopausal breast tissue. ? Mean ADC values did not vary significantly with menstrual cycle. ? Low postmenopausal ADC values may hinder tumour detection on DW-MRI.     

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.     

Diagnostic accuracy of diffusion weighted imaging for differentiation of supratentorial pilocytic astrocytoma and pleomorphic xanthoastrocytoma

Purpose

Supratentorial pilocytic astrocytoma (PA) may mimic pleomorphic xanthoastrocytoma (PXA) on conventional MR imaging, and a differentiation is clinically important because of distinct recurrence rate and anaplastic transformation rate. The purpose of this study was to investigate the diagnostic potential of diffusion-weighted imaging (DWI) in differentiating supratentorial PA from PXA.

Methods

We retrospectively reviewed DWI and conventional MR imaging of 16 patients with supratentorial PA and 8 patients with PXA. Variables of mean ADC values (ADC_mean) and minimum ADC values (ADC_min) were calculated from the ROIs containing the contrast-enhancing lesion on DWI. ADC_mean values and ADC_min values were compared among all supratentorial PA and PXA as well as between the subgroup of lobar PA and PXA by using an unpaired Student’s t test. The optimum threshold, sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC) were determined.

Results

Both ADC_mean values (1542?±?186 vs 1084?±?201?×?10^?6 mm²/s; P?<?0.001) and ADC_min values (1355?±?183 vs 988?±?180?×?10^?6 mm²/s; P?<?0.001) were significantly higher in supratentorial PA compared with PXA. The ADC_mean values and ADC_min values were also significantly higher in lobar PA than those in PXA. The ADC_mean values were useful for differentiating supratentorial PA from PXA, with a threshold value of >?1189.8?×?10^?6 mm²/s (sensitivity, 93.8%; specificity, 100%). The optimal threshold values of >?1189.8?×?10^?6 mm²/s for ADC_mean values provide sensitivity and specificity of 85.7 and 100%, respectively, for discriminating lobar PA from PXA. The optimum threshold value for ADC_min was >?1063.5?×?10^?6 mm²/s.

Conclusion

DWI is helpful in characterization and differentiation of supratentorial PA from PXA.

     

Diffusion-weighted magnetic resonance imaging for assessment of lung lesions: repeatability of the apparent diffusion coefficient measurement

Purpose

To establish repeatability of apparent diffusion coefficients (ADCs) acquired from free-breathing diffusion-weighted magnetic resonance imaging (DW-MRI) in malignant lung lesions and investigate effects of lesion size, location and respiratory motion.

Methods

Thirty-six malignant lung lesions (eight patients) were examined twice (1- to 5-h interval) using T1-weighted, T2-weighted and axial single-shot echo-planar DW-MRI (b?=?100, 500, 800 s/mm²) during free-breathing. Regions of interest around target lesions on computed b?=?800 s/mm² images by two independent observers yielded ADC values from maps (pixel-by-pixel fitting using all b values and a mono-exponential decay model). Intra- and inter-observer repeatability was assessed per lesion, per patient and by lesion size (> or <2 cm) or location.

Results

ADCs were similar between observers (mean ± SD, 1.15?±?0.28?×?10^-3 mm²/s, observer 1; 1.15?±?0.29?×?10^-3 mm²/s, observer 2). Intra-observer coefficients of variation of the mean [median] ADC per lesion and per patient were 11 % [11.4 %], 5.7 % [5.7 %] for observer 1 and 9.2 % [9.5 %], 3.9 % [4.7 %] for observer 2 respectively; inter-observer values were 8.9 % [9.3 %] (per lesion) and 3.0 % [3.7 %] (per patient). Inter-observer coefficient of variation (CoV) was greater for lesions <2 cm (n?=?20) compared with >2 cm (n?=?16) (10.8 % vs 6.5 % ADC_mean, 11.3 % vs 6.7 % ADC_median) and for mid (n?=?14) vs apical (n?=?9) or lower zone (n?=?13) lesions (13.9 %, 2.7 %, 3.8 % respectively ADC_mean; 14.2 %, 2.8 %, 4.7 % respectively ADC_median).

Conclusion

Free-breathing DW-MRI of whole lung achieves good intra- and inter-observer repeatability of ADC measurements in malignant lung tumours.

Key Points

? Diffusion-weighted MRI of the lung can be satisfactorily acquired during free-breathing ? DW-MRI demonstrates high contrast between primary and metastatic lesions and normal lung ? Apparent diffusion coefficient (ADC) measurements in lung tumours are repeatable and reliable ? ADC offers potential in assessing response in lung metastases in clinical trials     

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.     

Multiple antiplatelet therapy contributes to the reversible high signal spots on diffusion-weighted imaging in elective coiling of unruptured cerebral aneurysm

Introduction

Our aim was to systematically investigate radiographic characteristics and outcome of diffusion-weighted imaging (DWI) changes in the elective coiling of unruptured cerebral aneurysm with analyzing the correlation of antiplatelet therapy (APT).

Methods

In a total of 34 consecutive patients with unruptured cerebral aneurysms initially treated by coiling without stent assist, 26 (76.5 %) had DWI changes with 91 high signal spots within 24–48 h after the procedure. We recorded DWI parameters (location, volume, mean, and minimum values of the apparent diffusion coefficient: expressed as ADC_AVE and ADC_MIN) for each lesion, and evaluated its radiographic outcome on conventional MRI at follow-up (interval, 58.4?±?37.2 days) in the modes of APT.

Results

All patients with DWI high spots had no clinical symptoms. There was a strong correlation between ADC_AVE and ADC_MIN (r?=?0.82, p?<?0.0001). The mean ADC_AVE and rADC_AVE were 0.74?±?0.14?×?10^?3?mm²/s and 87?±?10 %. DWI high spots were small with a mean volume of 0.13?±?0.12 cm³, ranging from 0.04 to 0.86 cm³. A negative correlation was observed between the volume and values of ADC_AVE (r?=??0.48, p?<?0.0001). The DWI volume was significantly larger in single APT than in multiple (0.15?±?0.14 versus 0.10?±?0.07 cm³, p?=?0.0091). The permanent signal change was more observed in single APT than in multiple (24.5 % versus 5.2 %, p?=?0.02).

Conclusion

DWI high spots after elective coiling were small without significant decrease of ADC, and do not correspond to brain infarction. Periprocedural use of multiple antiplatelet agents is expected to reduce the volume of thromboembolism and permanent tissue damages.     

Grading of supratentorial astrocytic tumors by using the difference of ADC value

Introduction

To investigate the application value of diffusion-weighted imaging (DWI), the difference of apparent diffusion coefficient (ADC_difference) value calculated from ADC_difference map was used, in evaluating the pathologic grade of astrocytic tumors.

Methods

33 patients with histopathologically proven supratentorial astrocytic tumors were included in this prospective study. All of them received conventional magnetic resonance imaging (MRI), DWI with diffusion factor of 0 and 50?s/mm² and of 0 and 3,000?s/mm², and perfusion-weighted imaging (PWI) examinations. Pseudo-color ADC_difference maps were obtained by means of using ADC map with low b value (0 and 50?s/mm²) minus ADC map with high b value (0 and 3,000?s/mm²).

Results

The highest ADC_difference value of grades I?CII, grade III, and grade IV was (0.91?±?0.07)?×?10^?3, (1.81?±?0.38)?×?10^?3, and (2.36?±?0.32)?×?10^?3 mm²/s, respectively, and there was statistical difference among them (p?<?0.001). The highest ADC_difference value between low-grade (grades I?CII) and high-grade (grades III?CIV) astrocytic tumors showed statistical difference as well (p?<?0.001). The highest ADC_difference value of astrocytic tumors correlated positively with the pathologic grade of tumor (r?=?0.853, p?<?0.001). Positive correlation was found between the highest ADC_difference value and maximum relative cerebral blood volume (rCBV) value (r?=?0.829, p?<?0.001) in high-grade astrocytic tumors; however, the highest ADC_difference value and maximum rCBV value had no significant correlation in low-grade astrocytic tumors (r?=?0.259, p?=?0.536).

Conclusion

Quantitative analysis of highest ADC_difference value of supratentorial astrocytic tumors may provide valuable information of tumor microcirculation and perfusion, thus allowing a promising new method for preoperatively assessing the pathologic grade of tumor.     

Prognostic value of FDG-PET and DWI in breast cancer

Objective

To investigate the prognostic value of preoperative FDG-PET/CT and diffusion weighted imaging (DWI) in patients with breast cancer.

Methods

A total of 73 patients with newly diagnosed invasive breast cancer who had undergone preoperative whole-body FDG-PET/CT and 3-Tesla breast MRI including DWI followed by surgery were identified. Effects of primary tumor PET parameters [maximum standardized uptake value (SUV_max), mean SUV (SUV_mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] and DWI parameters [mean apparent diffusion coefficient (ADC_mean) and minimum ADC (ADC_min)] including clinicopathologic factors on disease-free survival (DFS) were retrospectively evaluated using the log-rank and Cox methods.

Results

After a median overall follow-up of 32.3 months in all patients, 6 (8.2%) of the 73 patients had recurrence. Receiver operating characteristic curve analysis and log-rank tests showed that patients with a high primary tumor SUV_max (≥?3.60), MTV (≥?3.15), and TLG (≥?16.0) had a significantly lower DFS rate than those with a low SUV_max (<?3.60), MTV (<?3.15), and TLG (<?16.0), respectively (p?=?0.0054, p?=?0.0054, and p?<?0.0001, respectively). SUV_mean, ADC_mean, and ADC_min were not significantly associated with recurrence. Univariate analysis showed that SUV_max (p?=?0.0054), MTV (p?=?0.0054), TLG (p?<?0.0001), tumor size (p?=?0.0083), estrogen receptor negativity (p?=?0.046), progesterone receptor negativity (p?=?0.0023), human epidermal growth factor receptor 2 positivity (p?=?0.043), and the presence of axillary lymph node metastasis (p?=?0.0037) were also significantly associated with recurrence. However, in multivariate analysis, none of them were an independent factor.

Conclusions

The preoperative SUV_max, MTV, and TLG of primary breast cancer are prognostic factors for recurrence, whereas ADC values are not.

     

Diffusion weighted MRI and 18F-FDG PET/CT in non-small cell lung cancer (NSCLC): Does the apparent diffusion coefficient (ADC) correlate with tracer uptake (SUV)?

Introduction

To investigate the potential correlation of the apparent diffusion coefficient assessed by diffusion-weighted MRI (DWI) and glucose metabolism determined by the standardized uptake value (SUV) at 18F-FDG PET/CT in non-small cell lung cancer (NSCLC).

Materials and methods

18F-FDG PET/CT and DWI (TR/TE, 2000/66 ms; b-values, 0 and 500 s/mm²) were performed in 41 consecutive patients with histologically verified NSCLC. Analysing the PET-CT data calculation of the mean (SUV_mean) and maximum (SUV_max) SUV was performed. By placing a region-of-interest (ROI) encovering the entire tumor mean (ADC_mean) and minimum ADC (ADC_min) were determined by two independent radiologists. Results of 18F-FDG PET-CT and DWI were compared on a per-patient basis. For statistical analysis Pearson's correlation coefficient, Bland–Altman and regression analysis were assessed.

Results

Data analysis revealed a significant inverse correlation of the ADC_min and SUV_max (r = −0.46; p = 0.032). Testing the correlation of the ADC_min and SUV_max for each histological subtype separately revealed that the inverse correlation was good for both adenocarcinomas (r = −0.47; p = 0.03) and squamouscell carcinomas (r = −0.71; p = 0.002), respectively. No significant correlation was found for the comparison of ADC_min and SUV_mean (r = −0.29; p = 0.27), ADC_mean vs. SUV_mean (r = −0.28; p = 0.31) or ADC_mean vs. SUV_max (r = −0.33; p = 0.23). The κ-value of 0.88 indicated a good agreement between both observers.

Conclusion

This preliminary study is the first to verify the relation between the SUV and the ADC in NSCLC. The significant inverse correlation of these two quantitative imaging approaches points out the association of metabolic activity and tumor cellularity. Therefore, DWI with ADC measurement might represent a new prognostic marker in NSCLC.     

Usefulness of MRI-assisted metabolic volumetric parameters provided by simultaneous <Superscript>18</Superscript>F-fluorocholine PET/MRI for primary prostate cancer characterization

Purpose

The aim of this study was to determine the usefulness of MRI-assisted positron emission tomography (PET) parameters provided by simultaneous ¹⁸F-fluorocholine (FCH) PET/MRI for characterization of primary prostate cancer.

Methods

Thirty patients with localized prostate cancer (mean age 69.4?±?6.7 years) confirmed by biopsy were prospectively enrolled for simultaneous PET/MRI imaging. The patients underwent ¹⁸F-FCH PET/MRI 1 week before undergoing total prostatectomy. Multiple parameters of diffusion-weighted MRI [minimum and mean apparent diffusion coefficient (ADC_min and ADC_mean)], metabolic PET [maximum and mean standardized uptake value (SUV_max and SUV_mean)], and metabolic volumetric PET [metabolic tumor volume (MTV) and uptake volume product (UVP)] were compared with laboratory, pathologic, and immunohistochemical (IHC) features of the prostate cancer specimen. PET parameters were divided into two categories as follows: volume of interest (VOI) of prostate by SUV cutoff 2.5 (SUV_max, SUV_mean, MTV_SUV, and UVP_SUV) and MRI-assisted VOI of prostate cancer (SUV_maxMRI, SUV_meanMRI, MTV_MRI, and UVP_MRI).

Results

The rates of prostate cancer-positive cases identified by MRI alone, ¹⁸F-FCH PET alone, and ¹⁸F-FCH PET/MRI were 83.3, 80.0, and 93.3 %, respectively. Among the multiple PET/MRI parameters, MTV_MRI showed fair correlation with serum prostate-specific antigen (PSA; r?=?0.442, p?=?0.014) and highest correlation with tumor volume (r?=?0.953, p?<?0.001). UVP_MRI showed highest correlation with serum PSA (r?=?0.531, p?=?0.003), good correlation with tumor volume (r?=?0.908, p?<?0.001), and it was significantly associated with Gleason score (p?=?0.041). High MTV_MRI and UVP_MRI values were significant for perineural invasion, lymphatic invasion, extracapsular extension, seminal vesicle invasion, and positive B-cell lymphoma 2 (Bcl-2) expression (all p?<?0.05).

Conclusion

Simultaneous ¹⁸F-FCH PET/MRI demonstrated a better diagnostic value for localized prostate cancer detection than each individual modality. MRI-assisted metabolic volumetric PET parameters (MTV_MRI and UVP_MRI) provided more accurate characterization of prostate cancer than conventional PET and MRI parameters.

     

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.     

Twins in spirit part II: DOTATATE and high-affinity DOTATATE—the clinical experience

Purpose

Over recent decades interest in diagnosis and treatment of neuroendocrine tumours (NET) has steadily grown. The basis for diagnosis and therapy of NET with radiolabelled somatostatin (hsst) analogues is the variable overexpression of hsst receptors (hsst1–5 receptors). We hypothesized that radiometal derivatives of DOTA-iodo-Tyr³-octreotide analogues might be excellent candidates for somatostatin receptor imaging. We therefore explored the diagnostic potential of ⁶⁸Ga-DOTA-iodo-Tyr³-octreotate [⁶⁸Ga-DOTA,3-iodo-Tyr³,Thr⁸]octreotide (⁶⁸Ga-HA-DOTATATE; HA, high-affinity) compared to the established ⁶⁸Ga-DOTA-Tyr³-octreotate (⁶⁸Ga-DOTATATE) in vivo.

Methods

The study included 23 patients with known somatostatin receptor-positive metastases from NETs, thyroid cancer or glomus tumours who were investigated with both ⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE. A patient-based and a lesion-based comparative analysis was carried out of normal tissue distribution and lesion detectability in a qualitative and a semiquantitative manner.

Results

⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE showed comparable uptake in the liver (SUV_mean 8.9?±?2.2 vs. 9.3?±?2.5, n.s.), renal cortex (SUV_mean 13.3?±?3.9 vs. 14.5?±?3.7, n.s.) and spleen (SUV_mean 24.0?±?6.7 vs. 22.9?±?7.3, n.s.). A somewhat higher pituitary uptake was found with ⁶⁸Ga-HA-DOTATATE (SUV_mean 6.3?±?1.8 vs. 5.4?±?2.1, p?<?0.05). On a lesion-by-lesion basis a total of 344 lesions were detected. ⁶⁸Ga-HA-DOTATATE demonstrated 328 lesions (95.3 % of total lesions seen), and ⁶⁸Ga-DOTATATE demonstrated 332 lesions (96.4 %). The mean SUV_max of all lesions was not significantly different between ⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE (17.8?±?11.4 vs. 16.7?±?10.7, n.s.).

Conclusion

Our analysis demonstrated very good concordance between ⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE PET data. As the availability and use of ⁶⁸Ga-HA-DOTATATE is not governed by patent restrictions it may be an attractive alternative to other ⁶⁸Ga-labelled hsst analogues.     

Pilot prospective evaluation of <Superscript>18</Superscript>F-FPPRGD<Subscript>2</Subscript> PET/CT in patients with cervical and ovarian cancer

Purpose

We report the effect of antiangiogenic therapy on the biodistribution of ¹⁸F-FPPRGD₂ (a surrogate biomarker of integrin α_vβ₃ expression), and the potential of ¹⁸F-FPPRGD₂ to predict the prognosis in patients with cervical cancer and ovarian cancer in this clinical scenario.

Methods

Data from six women, age range 30 – 59 years (mean?±?SD 44.0?±?12.5 years), who had undergone a ¹⁸F-FPPRGD₂ PET/CT scan and bevacizumab-containing therapy were prospectively collected and analyzed. We compared baseline ¹⁸F-FPPRGD₂ and ¹⁸F-FDG uptake in the lesions and tumor-to-background (T/B) ratios. The maximum and mean ¹⁸F-FPPRGD₂ standardized uptake values (SUV_max and SUV_mean) were recorded for 13 normal organs, as well as in all the identified malignant lesions on the pretreatment scan and the 1-week post-treatment scan. We also measured changes in ¹⁸F-FPPRGD₂ uptake from before to 1 week after treatment_, and compared them to the changes in ¹⁸F-FDG uptake from before to 6 weeks after treatment. Treatment outcomes were correlated with these changes.

Results

The uptake in lesions and T/B ratio of ¹⁸F-FPPRGD₂ were lower than those of ¹⁸F-FDG (SUV_max 3.7?±?1.3 vs. 6.0?±?1.8, P?<?0.001; SUV_mean 2.6?±?0.7 vs. 4.2?±?1.3, P?<?0.001; T/B ratio based on SUV_max 2.4?±?1.0 vs. 2.6?±?1.0, P?<?0.04; T/B ratio based on SUV_mean 1.9?±?0.6 vs. 2.4?±?1.0, P?<?0.003). One patient did not return for the follow-up scan and in another patient no lesions were identified on the pretreatment scan. ¹⁸F-FPPRGD₂ uptake in lesions in the remaining four patients had significantly changed 1 week after treatment (SUV_mean 3.3?±?1.0 vs. 2.7?±?1.0, P?<?0.001), while uptake in all normal tissues analyzed was not affected by treatment. One patient with clinical disease progression had a decrease in lesional ¹⁸F-FPPRGD₂ SUV_mean of 1.6 % and in ¹⁸F-FDG SUV_mean of 9.4 %. Two patients with a clinical complete response to treatment had decreases in lesional ¹⁸F-FPPRGD₂ SUV_mean of 25.2 % and 25.0 % and in ¹⁸F-FDG SUV_mean of 6.1 % and 71.8 %. One patient with a clinical partial response had a decrease in lesional ¹⁸F-FPPRGD₂ SUV_mean of 7.9 % and in ¹⁸F-FDG SUV_mean of 76.4 %.

Conclusion

This pilot study showed that ¹⁸F-FPPRGD₂ and ¹⁸F-FDG provide independent information about the biology of ovarian and cervical cancers. Bevacizumab-containing therapy does not affect ¹⁸F-FPPRGD₂ uptake in normal organs, but does result in statistically significant changes in lesions. In addition, ¹⁸F-FPPRGD₂ may have potential for early prediction of response to such treatments. These preliminary findings have to be confirmed in larger studies.

     

Suppression of myocardial 18F-FDG uptake with a preparatory “Atkins-style” low-carbohydrate diet

Objectives

Physiological myocardial uptake of 18F-FDG during positron emission tomography can mask adjacent abnormal uptake in mediastinal malignancy and inflammatory cardiac diseases. Myocardial uptake is unpredictable and variable. This study evaluates the impact of a low-carbohydrate diet in reducing myocardial FDG uptake.

Method

Patients attending for clinically indicated oncological FDG PET were asked to have an “Atkins-style” low-carbohydrate diet (less than 3 g) the day before examination and an overnight fast. A total of 120 patients following low-carbohydrate diet plus overnight fast were compared with 120 patients prepared by overnight fast alone. Patients having an Atkins-style diet also completed a diet compliance questionnaire. SUV_max and SUV_mean for myocardium, blood pool and liver were measured in both groups.

Results

Myocardial SUV_max fell from 3.53?±?2.91 in controls to 1.77?±?0.91 in the diet-compliant group. 98 % of diet-compliant patients had a myocardial SUV_max less than 3.6 compared with 67 % of controls. Liver and blood pool SUV_max rose from 2.68?±?0.49 and 1.82?±?0.30 in the control group to 3.14?±?0.57 and 2.06?±?0.30.

Conclusion

An Atkins-style diet the day before PET, together with an overnight fast, effectively suppresses myocardial FDG uptake.

Key Points

? Low-carbohydrate diet (LCD) the day before PET suppresses myocardial FDG uptake. ? LCD before PET increases liver and blood pool SUV _max and SUV _mean . ? Suppression of myocardial uptake may improve PET imaging of thoracic disease. ? Suppression of myocardial uptake may help imaging cardiac inflammatory disease with PET.     

Diffusion-weighted MR imaging in primary rectal cancer staging demonstrates but does not characterise lymph nodes

Objectives

To evaluate the performance of diffusion-weighted MRI (DWI) for the detection of lymph nodes and for differentiating between benign and metastatic nodes during primary rectal cancer staging.

Methods

Twenty-one patients underwent 1.5-T MRI followed by surgery (± preoperative 5?×?5 Gy). Imaging consisted of T2-weighted MRI, DWI (b0, 500, 1000), and 3DT1-weighted MRI with 1-mm isotropic voxels. The latter was used for accurate detection and per lesion histological validation of nodes. Two independent readers analysed the signal intensity on DWI and measured the mean apparent diffusion coefficient (ADC) for each node (ADC_node) and the ADC of each node relative to the mean tumour ADC (ADC_rel).

Results

DWI detected 6 % more nodes than T2W-MRI. The signal on DWI was not accurate for the differentiation of metastatic nodes (AUC 0.45–0.50). Interobserver reproducibility for the nodal ADC measurements was excellent (ICC 0.93). Mean ADC_node was higher for benign than for malignant nodes (1.15?±?0.24 vs. 1.04?±?0.22 *10^-3 mm²/s), though not statistically significant (P?=?0.10). Area under the ROC curve/sensitivity/specificity for the assessment of metastatic nodes were 0.64/67 %/60 % for ADC_node and 0.67/75 %/61 % for ADC_rel.

Conclusions

DWI can facilitate lymph node detection, but alone it is not reliable for differentiating between benign and malignant lymph nodes.

Key Points

? Diffusion-weighted (DW) magnetic resonance imaging (MRI) offers new information in rectal cancer. ? DW MRI demonstrates more lymph nodes than standard T2-weighted MRI. ? Visual DWI assessment does not discriminate between benign and metastatic nodes. ? Apparent diffusion coefficients do not discriminate between benign and metastatic nodes.     

Voxel-wise correlation of functional imaging parameters in HNSCC patients receiving PET/MRI in an irradiation setup

Purpose

The purpose of this study was to demonstrate the feasibility of voxel-wise multiparametric characterization of head and neck squamous cell carcinomas (HNSCC) using hybrid multiparametric magnetic resonance imaging and positron emission tomography with [¹⁸F]-fluorodesoxyglucose (FDG-PET/MRI) in a radiation treatment planning setup.

Methods

Ten patients with locally advanced HNSCC were examined with a combined FDG-PET/MRI in an irradiation planning setup. The multiparametric imaging protocol consisted of FDG-PET, T2-weighted transverse short tau inversion recovery sequence (STIR) and diffusion-weighted MRI (DWI). Primary tumours were manually segmented and quantitative imaging parameters were extracted. PET standardized uptake values (SUV) and DWI apparent diffusion coefficients (ADC) were correlated on a voxel-wise level.

Results

Images acquired in this specialised radiotherapy planning setup achieved good diagnostic quality. Median tumour volume was 4.9 [1.1–42.1]?ml. Mean PET SUV and ADC of the primary tumours were 5?±?2.5 and 1.2?±?0.3 10^?3?mm²/s, respectively. In voxel-wise correlation between ADC values and corresponding FDG SUV of the tumours, a significant negative correlation was observed (r?=??0.31?±?0.27, p?<?0.05).

Conclusion

Multiparametric voxel-wise characterization of HNSCC is feasible using combined PET/MRI in a radiation planning setup. This technique may provide novel insights into tumour biology with regard to radiation therapy in the future.

     

A prospective clinical study of 18 F-FAZA PET-CT hypoxia imaging in head and neck squamous cell carcinoma before and during radiation therapy

Purpose

Hypoxia in head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis and outcome. ¹⁸?F-Fluoroazomycin arabinoside (FAZA) is a positron emission tomography (PET) tracer developed to enable identification of hypoxic regions within tumor. The aim of this study was to evaluate the use of ¹⁸ F-FAZA-PET for assessment of hypoxia before and during radiation therapy.

Methods

Twelve patients with locally advanced HNSCC underwent ¹⁸ F-FAZA-PET scans before and at fraction 7 and 17 of concomitant chemo-radiotherapy. A hypoxic voxel was defined as a voxel expressing a standardized uptake value (SUV) equal or above the SUV_mean of the posterior contralateral neck muscles plus three standard deviations. The fractional hypoxic volume fraction (FHV) and the spatial move of hypoxic volumes during treatment were analyzed.

Results

A hypoxic volume could be identified in ten patients before treatment. FAZA-PET FHV varied from 0 to 54.3 % and from 0 to 41.4 % in the primary tumor and in the involved node, respectively. Six out of these ten patients completed all the FAZA-PET-computed tomography (CT) during the radiotherapy. In all patients, FHV and SUV_max values decreased. All patient presented a spatial move of hypoxic volume, but only three patients had newborn hypoxic voxels after 17 fractions.

Conclusion

This study indicated that ¹⁸?F-FAZA-PET could be used to identify and quantify tumor hypoxia before and during concomitant radio-chemotherapy in patients with locally advanced HNSCC. In addition to the information on prognostic value, the use of ¹⁸?F-FAZA-PET allowed the delineation of hypoxic volumes for dose escalation protocols. However, due to fluctuation of hypoxia during treatment, repeated scan will have to be performed (i.e. adaptive radiotherapy).     

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.