Abstract The integrin alpha v beta 3 plays an important role in angiogenesis and tumor metastasis. It is expressed on activated endothelial cells as well as some tumor cells. Therefore it is a ...promising imaging target as a potential surrogate parameter of angiogenic activity. Molecular imaging of alpha v beta 3 expression could potentially facilitate response evaluation of antiangiogenic drugs (e. g. bevacizumab) or aid in selecting and monitoring patients receiving humanized monoclonal antibody therapies directed against alpha v beta 3 (EMD121974). Therefore many different approaches for imaging of alpha v beta 3 expression have been studied in the recent years, including positron emission tomography (PET), single photon emission tomography (SPECT), magnetic resonance imaging (MRI), optical imaging and ultrasound using targeted microbubbles. While optical imaging techniques lend themselves for preclinical studies, PET and SPECT using the alpha v beta 3 specific tracers 18Fgalacto-RGD and 99mTcNC100692 are the only techniques up to now which have been successfully used in patients. The various advantages and disadvantages of several imaging techniques will be discussed in this article.
Current standard imaging techniques are insufficient to reliably detect lymph node metastases in prostate cancer. Recently ligands of PSMA (prostate specific membrane antigen) were introduced in PET ...(positron emission tomography) of prostate cancer. Thus the aims of this retrospective analysis were to 1) investigate the diagnostic efficacy of (68)Ga-PSMA-PET imaging for lymph node staging in patients with prostate cancer scheduled for radical prostatectomy and 2) compare it to morphological imaging (computerized tomography and magnetic resonance tomography) with histopathological evaluation as the standard of reference.
A total of 130 patients with intermediate to high risk prostate cancer were staged with (68)Ga-PSMA-PET/magnetic resonance tomography or PET/computerized tomography from December 2012 to November 2014 before radical prostatectomy and template pelvic lymph node dissection. Histopathological findings of resected tissue were statistically correlated with the results of (68)Ga-PSMA-PET and morphological imaging in a patient and template based manner.
Lymph node metastases were found in 41 of 130 patients (31.5%). On patient based analysis the sensitivity, specificity and accuracy of (68)Ga-PSMA-PET were 65.9%, 98.9% and 88.5%, and those of morphological imaging were 43.9%, 85.4% and 72.3%, respectively. Of 734 dissected lymph node templates 117 (15.9%) showed metastases. On template based analysis the sensitivity, specificity and accuracy of (68)Ga-PSMA-PET were 68.3%, 99.1% and 95.2%, and those of morphological imaging were 27.3%, 97.1% and 87.6%, respectively. On ROC analysis (68)Ga-PSMA-PET performed significantly better than morphological imaging alone on patient and template based analyses (p = 0.002 and <0.001, respectively).
In patients with intermediate to high risk prostate cancer preoperative lymph node staging with (68)Ga-PSMA-PET proved to be superior to standard routine imaging. Thus it has the potential to replace current standard imaging for this indication if confirmed by prospective studies.
The purpose of this study was to evaluate the accuracy of Glu-NH-CO-NH-Lys-(Ahx)-
Ga(HBED-CC) PET compared with morphologic imaging for the assessment of lymph node metastases (LNM) in patients with ...recurrent prostate cancer.
Forty-eight patients (median age, 71 y; interquartile range, 66-74 y) with biochemical recurrence (median prostate-specific antigen level, 1.31 ng/mL; interquartile range, 0.75-2.55 ng/mL) who underwent
Ga-prostate-specific membrane antigen (PSMA) HBED-CC PET/CT or PET/MR and salvage lymphadenectomy were retrospectively included. Institutional review board approval and written informed consent were obtained from all patients for the purpose of anonymized evaluation and publication of their data. Standardized predefined lymph node (LN) template fields (n = 10) were evaluated in
Ga-PSMA HBED-CC PET and morphologic imaging for the presence of LNM using a 5-point-scale. Additionally, SUV
and size of suspicious lesions were determined. Specificity of
Ga-PSMA HBED-CC PET imaging for PET-positive LNs was defined by comparison to histopathology. The diagnostic accuracy of
Ga-PSMA HBED-CC PET compared with morphologic imaging alone was assessed, and areas under the receiver-operating-characteristic curves are presented.
LNM were found histologically in 68 of 179 resected anatomic LN fields (38.0%). The specificity of
Ga-PSMA HBED-CC PET and morphologic imaging was 97.3% and 99.1%, respectively. However,
Ga-PSMA HBED-CC PET detected LNM in 53 of 68 histopathologically proven metastatic LN fields (77.9%) whereas morphologic imaging was positive in only 18 of 67 (26.9%).
Ga-PSMA HBED-CC PET imaging performed significantly superior to morphologic imaging for detection of LNM (difference in the areas under the receiver-operating-characteristic curves, 0.139; 95% confidence interval, 0.063-0.214; P < 0.001). In
Ga-PSMA HBED-CC PET, the mean size of PET-positive LN measured by CT or MRI was 8.3 ± 4.3 mm (range, 4-25 mm), and LNs, which were suspicious only in CT or MRI, presented with a mean size of 13.0 ± 4.9 mm (range, 8-25 mm).
Ga-PSMA HBED-CC PET imaging is a promising method for early detection of LNM in patients with biochemical recurrent prostate cancer. It is more accurate than morphologic imaging and thus might represent a valuable tool for guiding salvage lymphadenectomy.
The significant advances in magnetic resonance imaging (MRI) hardware and software, sequence design, and postprocessing methods have made diffusion‐weighted imaging (DWI) an important part of body ...MRI protocols and have fueled extensive research on quantitative diffusion outside the brain, particularly in the oncologic setting. In this review, we summarize the most up‐to‐date information on DWI acquisition and clinical applications outside the brain, as discussed in an ISMRM‐sponsored symposium held in April 2015. We first introduce recent advances in acquisition, processing, and quality control; then review scientific evidence in major organ systems; and finally describe future directions. J. Magn. Reson. Imaging 2016;44:521–540.
The recently introduced first integrated whole-body PET/MR scanner allows simultaneous acquisition of PET and MRI data in humans and, thus, may offer new opportunities, particularly regarding ...diagnostics in oncology. This scanner features major technologic differences from conventional PET/CT devices, including the replacement of photomultipliers with avalanche photodiodes and the need for MRI-based attenuation correction. The aim of this study was to evaluate the comparability of clinical performance between conventional PET/CT and PET/MR in patients with oncologic diseases.
Thirty-two patients with different oncologic diagnoses underwent a single-injection, dual-imaging protocol consisting of a PET/CT and subsequent PET/MR scan. PET/CT scans were performed according to standard clinical protocols (86 ± 8 min after injection of 401 ± 42 MBq of (18)F-FDG, 2 min/bed position). Subsequently (140 ± 24 min after injection), PET/MR was performed (4 min/bed position). PET images of both modalities were reconstructed iteratively. Attenuation and scatter correction as well as regional allocation of PET findings were performed using low-dose CT data for PET/CT and Dixon MRI sequences for PET/MR. PET/MR and PET/CT were compared visually by 2 teams of observers by rating the number and location of lesions suspicious for malignancy, as well as image quality and alignment. For quantitative comparison, standardized uptake values (SUVs) of the detected lesions and of different tissue types were assessed.
Simultaneous PET/MR acquisition was feasible with high quality in short acquisition time (≤ 20 min). No significant difference was found between the numbers of suspicious lesions (n = 80) or lesion-positive patients (n = 20) detected with PET/MR or PET/CT. Anatomic allocation of PET/MR findings by means of the Dixon MRI sequence was comparable to allocation of PET/CT findings by means of low-dose CT. Quantitative evaluation revealed a high correlation between mean SUVs measured with PET/MR and PET/CT in lesions (ρ = 0.93) and background tissue (ρ = 0.92).
This study demonstrates, for what is to our knowledge the first time, that integrated whole-body PET/MR is feasible in a clinical setting with high quality and in a short examination time. The reliability of PET/MR was comparable to that of PET/CT in allowing the detection of hypermetabolic lesions suspicious for malignancy in patients with oncologic diagnoses. Despite different attenuation correction approaches, tracer uptake in lesions and background correlated well between PET/MR and PET/CT. The Dixon MRI sequences acquired for attenuation correction were found useful for anatomic allocation of PET findings obtained by PET/MR in the entire body. These encouraging results may form the foundation for future studies aiming to define the added value of PET/MR over PET/CT.
The aim of this study was to investigate the accuracy of single-time-point (STP) renal dosimetry imaging using SPECT/CT data, a nonlinear mixed-effects (NLME) model, and a population-based model ...selection (PBMS) in a large population for
Lu-labeled prostate-specific membrane antigen therapy.
Biokinetic data (mean ± SD) of
LuLu-PSMA-617 in kidneys at time points 1 (1.8 ± 0.8 h), 2 (18.7 ± 0.9 h), 3 (42.6 ± 1.0 h), 4 (66.3 ± 0.9 h), and 5 (160.3 ± 24.2 h) after injection were obtained from 63 patients with metastatic castration-resistant prostate cancer using SPECT/CT. Thirteen functions were derived from various parameterizations of 1- to 5-exponential functions. The function's parameters were fitted in the NLME framework to the all-time-point (ATP) data. The PBMS NLME method was performed using the goodness-of-fit test and Akaike weight to select the best function fitting the data. The best function from ATP fitting was used to calculate the reference time-integrated activity and absorbed doses. In STP dosimetry, the parameters of a particular patient with STP data were fitted simultaneously to the STP data at different time points of that patient with ATP data of all other patients. The parameters from STP fitting were used to calculate the STP time-integrated activity and absorbed doses. Relative deviations (RDs) and root-mean-square errors (RMSEs) were used to analyze the accuracy of the calculated STP absorbed dose compared with the reference absorbed dose obtained from the best-fit ATP function. The performance of STP dosimetry using PBMS NLME modeling was compared with the Hänscheid and Madsen methods.
The function Formula: see text was selected as the best-fit ATP function, with an Akaike weight of 100%. For STP dosimetry, the STP measurement by SPECT/CT at time point 3 (42.6 ± 1.0 h) showed a relatively low mean RD of -4.4% ± 9.4% and median RD of -0.7%. Time point 3 had the lowest RMSE value compared with those at the other 4 time points. The RMSEs of the absorbed dose RDs for time points 1-5 were 23%, 16%, 10%, 20%, and 53%, respectively. The STP dosimetry using the PBMS NLME method outperformed the Hänscheid and Madsen methods for all investigated time points.
Our results show that a single measurement of SPECT/CT at 2 d after injection might be used to calculate accurate kidney-absorbed doses using the NLME method and PBMS.
Fully integrated PET/MR imaging holds great promise as a novel hybrid imaging modality in oncology and might offer advantages to PET/CT in many instances, especially because of the superior ...soft-tissue contrast of MR imaging, compared with CT. However, lung metastases are a frequent finding in oncologic patients, and for imaging of the lung CT is still the modality of choice. Thus, we prospectively evaluated differences in quality, detection rate, size, and radiotracer uptake of pulmonary lesions in (18)F-FDG PET/CT and PET/MR imaging.
Institutional review board approval and informed consent were obtained. Forty patients (23 men, 17 women; mean age ± SD, 53.2 ± 13.1 y) underwent a single-injection dual-imaging protocol with (18)F-FDG PET/CT and PET/MR imaging. Pulse sequences for the lung included T1-weighted VIBE (volumetric interpolated breath-hold examination) Dixon for attenuation correction and contrast-enhanced VIBE pulse sequences. All patients underwent a diagnostic CT of the chest in deep inspiration, which also served as a standard of reference. Two masked readers assessed in consensus all images randomly concerning quality, detection, standardized uptake value (SUV), and size of pulmonary nodules. Correlations were performed using linear correlation.
Overall, 47 pulmonary lesions (mean size ± SD, 10.0 ± 11.4 mm; range, 2-60 mm) in 25 of 40 patients were detected. The PET datasets of PET/MR imaging and PET/CT revealed 22 of 47 pulmonary lesions with focal (18)F-FDG uptake. SUVs of lung lesions in PET/MR imaging and PET/CT correlated significantly (R = 0.9; P = 0.0001) and showed no significant difference (mean SUV PET/MR imaging, 6.3; PET/CT, 5.1; P = 0.388). There was a significantly lower image quality comparing Dixon and VIBE sequence with CT whereas PET from PET/CT and PET from PET/MR imaging showed the same results (2.8). Dixon images detected 15 of 47 lung lesions whereas VIBE images detected 32 of 47 lesions, respectively. The detection rates for small lung lesions less than 1 cm in diameter (n = 33) of MR imaging was significantly lower, with a detection rate of 9 of 33 for the Dixon sequence and 15 of 33 for the VIBE sequence (P < 0.0001 for VIBE and Dixon sequence). There was a high correlation of pulmonary lesion size of CT versus VIBE (R = 0.97).
PET image quality and detection rate of (18)F-FDG-positive lung lesions in PET/MR imaging is equivalent to PET/CT despite differences in attenuation-correction techniques. Additionally, a high linear correlation coefficient in the SUVs for the PET images from PET/CT and PET/MR imaging was found. The detection rate of lung lesions can be significantly improved by adding a diagnostic contrast-enhanced VIBE sequence to the PET/MR imaging protocol. However, the detection rate of small lung lesions is still inferior, compared with PET/CT with diagnostic CT of the chest.
Personalized treatment planning in Molecular Radiotherapy (MRT) with accurately determining the absorbed dose is highly desirable. The absorbed dose is calculated based on the Time-Integrated ...Activity (TIA) and the dose conversion factor. A crucial unresolved issue in MRT dosimetry is which fit function to use for the TIA calculation. A data-driven population-based fitting function selection could help solve this problem. Therefore, this project aims to develop and evaluate a method for accurately determining TIAs in MRT, which performs a Population-Based Model Selection within the framework of the Non-Linear Mixed-Effects (NLME-PBMS) model.
Biokinetic data of a radioligand for the Prostate-Specific Membrane Antigen (PSMA) for cancer treatment were used. Eleven fit functions were derived from various parameterisations of mono-, bi-, and tri-exponential functions. The functions' fixed and random effects parameters were fitted (in the NLME framework) to the biokinetic data of all patients. The goodness of fit was assumed acceptable based on the visual inspection of the fitted curves and the coefficients of variation of the fitted fixed effects. The Akaike weight, the probability that the model is the best among the whole set of considered models, was used to select the fit function most supported by the data from the set of functions with acceptable goodness of fit. NLME-PBMS Model Averaging (MA) was performed with all functions having acceptable goodness of fit. The Root-Mean-Square Error (RMSE) of the calculated TIAs from individual-based model selection (IBMS), a shared-parameter population-based model selection (SP-PBMS) reported in the literature, and the functions from NLME-PBMS method to the TIAs from MA were calculated and analysed. The NLME-PBMS (MA) model was used as the reference as this model considers all relevant functions with corresponding Akaike weights.
The function f3a=A1e-λ1+λphyst+A2e-λphyst was selected as the function most supported by the data with an Akaike weight of (54 ± 11) %. Visual inspection of the fitted graphs and the RMSE values show that the NLME model selection method has a relatively better or equivalent performance than the IBMS or SP-PBMS methods. The RMSEs of the IBMS, SP-PBMS, and NLME-PBMS (f3a) methods are 7.4%, 8.8%, and 2.4%, respectively.
A procedure including fitting function selection in a population-based method was developed to determine the best fit function for calculating TIAs in MRT for a given radiopharmaceutical, organ and set of biokinetic data. The technique combines standard practice approaches in pharmacokinetics, i.e. an Akaike-weight-based model selection and the NLME model framework.
Objectives The goal of this study was to evaluate the feasibility of 18 FGalacto-RGD positron emission tomography (PET)/computed tomography (CT) imaging of αvβ3 expression in human carotid plaques. ...Background The integrin αvβ3 is expressed by macrophages and angiogenic endothelial cells in atherosclerotic lesions and thus is a marker of plaque inflammation and, potentially, of plaque vulnerability. 18 FGalacto-RGD is a PET tracer binding specifically to αvβ3. Therefore, 18 FGalacto-RGD PET/CT imaging of αvβ3 expression in human carotid plaques might provide a novel noninvasive biomarker of plaque vulnerability. Methods 18 FGalacto-RGD PET/CT imaging was performed in 10 patients with high-grade carotid artery stenosis scheduled for carotid endarterectomy. Tracer uptake was measured in the stenotic areas of the carotid arteries, as well as on the contralateral side, and was corrected for blood pool activity, measured in the distal common carotid artery (target-to-background TB ratio). TB ratio was correlated with immunohistochemistry of αvβ3 expression (LM609), macrophage density (CD68), and microvessel density (CD31) of the surgical specimen. In addition, ex vivo autoradiography of the surgical specimen with 18 FGalacto-RGD and competition experiments with an unlabeled αvβ3-specific RGD peptide were performed. Results 18 FGalacto-RGD PET/CT showed significantly higher TB ratios in stenotic areas compared with nonstenotic areas (p = 0.01). TB ratios correlated significantly with αvβ3 expression (R = 0.787, p = 0.026) and intensity of ex vivo autoradiography (R = 0.733, p = 0.038). Binding to atherosclerotic plaques was efficiently blocked in ex vivo competition experiments. A weak-to-moderate correlation was found with macrophage density (R = 0.367, p = 0.299) and microvessel density (R = 0.479, p = 0.176), which did not reach statistical significance. Conclusions 18 FGalacto-RGD PET/CT shows specific tracer accumulation in human atherosclerotic carotid plaques, which correlates with αvβ3 expression. Based on these initial data, larger prospective studies are now warranted to evaluate the potential of molecular imaging of αvβ3 expression for assessment of plaque inflammation in patients.
In this retrospective study we compared magnet resonance imaging (MRI) and computed tomography (CT) each combined with identical 2-deoxy-2-18F fluoro-D-glucose or 2-18F F-18 fluorodeoxyglucose (FDG) ...positron emission tomography (PET) data in patients with recurrent differentiated thyroid cancer (DTC). In total 42 patients with DTC were examined. All patients underwent FDG PET/MRI and CT, the latter originating from one of the following examinations: I-131 single photon emission computed tomography/CT (32/42), low dose FDG PET/CT (5/42) or diagnostic FDG PET/CT (5/42). Two readers assessed FDG PET/MRI as well as FDG PET/CT, with the latter CT coming from one of the above examinations performed at a maximum temporal interval of 5 days from PET/MRI. Local recurrence, cervical lymph node - and pulmonary metastases were assessed in a consensus read. Lesions rated with a high malignancy score (score 4 or 5) were further analyzed. Every malignant lesion was verified if it was identified by one of both or by both modalities. In 20 of 42 patients altogether 100 malignant lesions were present. In 11/20 patients in total 15 local recurrences (15 in MRI/ 9 in CT: 9 CT/MRI, 6 MRI only, 0 CT only; P = .04) were found with a statistically significant better performance of MRI. Regarding lymph node metastases, in total 13 lesions (12 in MRI/ 8 in CT: 7 CT/MRI, 5 MRI only, 1 CT only; P = .22) in 8/20 patients were found with no significant difference between both modalities. Furthermore, in 9/20 patients in total 72 lung lesions (40 in MRI/ 63 in CT: 31 CT/MRI, 9 MRI only, 32 CT only; P = .001) were found with a statistically significant better performance of CT. In 33/42 patients follow up was available and supported the observations. In patients with recurrent DTC, PET/MRI showed superiority compared to PET/CT in evaluation of the neck region. PET/MRI was inferior to PET/CT in evaluation of the lung. PET/MRI in combination with a low dose CT of the lung may thus represent the ideal staging tool in patients with recurrent DTC.
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