68Ga-Pentixafor PET/MRI for Treatment Response Assessment in Mantle Cell Lymphoma: Comparison Between Changes in Lesion CXCR4 Expression on PET and Lesion Size and Diffusivity on MRI.

PURPOSE: The aim of this study was to compare CXCR4 imaging with 68Ga-pentixafor PET to MRI for treatment response assessment in patients with mantle cell lymphoma (MCL). PATIENTS AND METHODS: Twenty-two posttreatment 68Ga-pentixafor PET/MRI scans of 16 patients (7 women and 9 men; mean age, 69.9 ± 7.9) with a total of 67 target lesions on baseline PET/MRI were analyzed. Rates of complete remission per lesion and per scan, according to MRI (based on lesion size) and 68Ga-pentixafor PET (based on SUV decrease to lower than liver and blood pool uptake), were compared using McNemar tests. The t tests and Pearson correlation coefficients (r) were used to compare rates of change in lesion diameter products (DPs) on MRI, and standardized uptake values (SUVmax, SUVmean) on PET, relative to baseline. RESULTS: At interim PET/MRI, 18/32 (56.3%) target lesions met CR criteria on 68Ga-pentixafor PET, and 16/32 (50.0%) lesions met size-based MRI criteria for CR (P = 0.63). At end-of-treatment PET/MRI, 40/57 (70.2%) target lesions met 68Ga-pentixafor PET criteria for CR, and 27/57 (47.4%) lesions met size-based MRI criteria for CR (P = 0.021). Complete remission after treatment was observed more frequently on 68Ga-pentixafor PET (11/22 scans, 54.5%) than on MRI (6/22 scans, 27.3%) (P = 0.031). Rates of change did not differ significantly between lesion DP (-69.20% ± 34.62%) and SUVmax (-64.59% ± 50.78%, P = 0.22), or DP and SUVmean (-60.15 ± 64.58, P = 0.064). Correlations were strong between DP and SUVmax (r = 0.71, P < 0.001) and DP and SUVmean (r = 0.73, P < 0.001). CONCLUSIONS: In MCL patients, 68Ga-pentixafor PET may be superior for assessment of complete remission status than anatomic MRI using lesion size criteria, especially at the end of treatment.

Comparing calculated and experimental activity and dose values obtained from image-based quantification of 90Y SPECT/CT Data.

PURPOSE: Selective internal radiation therapy (SIRT) is a treatment for various kinds of liver tumours by injecting 90Y bearing microspheres into the liver vessels. To perform meaningful post-treatment dosimetry, quantitative imaging is performed. METHODS: This work uses a Monte-Carlo based reconstruction software with scatter and attenuation correction and collimator modelling that allows the quantification of 90Y bremsstrahlung SPECT/CT data. A dataset comprising 17 patients and measurements on a Jaszczak phantom, a NEMA IEC Body phantom and an anthropomorphic liver phantom are analysed and activities and dose values are acquired. These measured values are compared with applied activities and pre-treatment calculations, allowing to assess the quality of the SPECT reconstruction. A detailed uncertainty budget is presented, including uncertainties of the dose calibrator, the count rate, non-included interactions and other factors. RESULTS: The applied method is validated by finding measurements repeatable within the given uncertainty, and it is shown the influence of various parameters on the reconstruction process is negligible. Furthermore, activities and doses measured in the phantoms show good agreement with calculated values, if they are corrected for partial volume effects. CONCLUSIONS: The strict observation of metrological requirements and the creation of an uncertainty budget increase the reliability and traceability of this novel approach to 90Y dosimetry. It gives an example of successful voxel-based dosimetry based on quantitative 90Y SPECT/CT image data.

Assessment of Central Nervous System Lymphoma Based on CXCR4 Expression In Vivo Using 68Ga-Pentixafor PET/MRI.

PURPOSE OF THE REPORT: F-FDG PET is limited for assessment of central nervous system lymphoma (CNSL) due to physiologic tracer accumulation in the brain. We prospectively evaluated the novel PET tracer Ga-pentixafor, which targets the C-X-C chemokine receptor 4 (CXCR4), for lesion visualization and response assessment of CNSL. MATERIALS AND METHODS: Seven CNSL patients underwent Ga-pentixafor PET/MRI with contrast enhancement (CE-MRI) and diffusion-weighted sequences. The accuracy of Ga-pentixafor PET for CNSL lesion detection relative to the CE-MRI reference standard was determined. Standardized uptake values (SUVmean and SUVmax), PET-based (PTV) and MRI-based (VOLMRI) tumor volumes, and apparent diffusion coefficients (ADCs) were assessed, and correlation coefficients were calculated. Three SUVmax thresholds (41%, 50%, and 70%) were evaluated for PTV definitions (PTV41%, PTV50%, and PTV70%) and tested against VOLMRI using paired sample t tests. RESULTS: Twelve Ga-pentixafor PET/MRI examinations (including 5 follow-up scans) of 7 patients were evaluated. Ga-pentixafor PET demonstrated 18 lesions, all of which were confirmed by CE-MRI; there were no false-positive lesions on PET (accuracy, 100%). PTV41% showed the highest concordance with lesion morphology, with no significant difference compared with VOLMRI (mean difference, -0.24 cm; P = 0.45). The correlation between ADCmean and SUVmean41% (r = 0.68) was moderate. Changes in PTV41% on follow-up PET/MRI showed the same trend as VOLMRI changes, including progression of 1 lesion each in patient 1 (+456.0% PTV41% and +350.8% VOLMRI) and patient 3 (+110.4% PTV41% and +85.1% VOLMRI). CONCLUSIONS: Ga-pentixafor PET may be feasible for assessment and follow-up of CNSL. Future studies need to focus on testing its clinical value to distinguish between glioma and CNSL, and between radiation-induced inflammation and viable residual tumor.

The Presence of Active Brown Adipose Tissue Determines Cold-Induced Energy Expenditure and Oxylipin Profiles in Humans.

BACKGROUND: Accumulating evidence links brown adipose tissue (BAT) to increased cold-induced energy expenditure (CIEE) and regulation of lipid metabolism in humans. BAT has also been proposed as a novel source for biologically active lipid mediators including polyunsaturated fatty acids (PUFAs) and oxylipins. However, little is known about cold-mediated differences in energy expenditure and various lipid species between individuals with detectable BAT positive (BATpos) and those without BAT negative (BATneg). METHODS: Here we investigated a unique cohort of matched BATpos and BATneg individuals identified by 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography ([18F]-FDG PET/CT). BAT function, CIEE, and circulating oxylipins, were analyzed before and after short-term cold exposure using [18F]-FDG PET/CT, indirect calorimetry, and high-resolution mass spectrometry, respectively. RESULTS: We found that active BAT is the major determinant of CIEE since only BATpos individuals experienced significantly increased energy expenditure in response to cold. A single bout of moderate cold exposure resulted in the dissipation of an additional 20 kcal excess energy in BATpos but not in BATneg individuals. The presence of BAT was associated with a unique systemic PUFA and oxylipin profile characterized by increased levels of anti-inflammatory omega-3 fatty acids as well as cytochrome P450 products but decreased concentrations of some proinflammatory hydroxyeicosatetraenoic acids when compared with BATneg individuals. Notably, cold exposure raised circulating levels of various lipids, including the recently identified BAT-derived circulating factors (BATokines) DiHOME and 12-HEPE, only in BATpos individuals. CONCLUSIONS: In summary, our data emphasize that BAT in humans is a major contributor toward cold-mediated energy dissipation and a critical organ in the regulation of the systemic lipid pool.

PET/MRI versus PET/CT in oncology: a prospective single-center study of 330 examinations focusing on implications for patient management and cost considerations.

PURPOSE: PET/MRI has recently been introduced into clinical practice. We prospectively investigated the clinical impact of PET/MRI compared with PET/CT, in a mixed population of cancer patients, and performed an economic evaluation of PET/MRI. METHODS: Cancer patients referred for routine staging or follow-up by PET/CT underwent consecutive PET/CT and PET/MRI, using single applications of [18F]FDG, [68Ga]Ga-DOTANOC, or [18F]FDOPA, depending on tumor histology. PET/MRI and PET/CT were rated separately, and lesions were assessed per anatomic region; based on regions, per-examination and per-patient accuracies were determined. A simulated, multidisciplinary team meeting served as reference standard and determined whether differences between PET/CT and PET/MRI affected patient management. The McNemar tests were used to compare accuracies, and incremental cost-effectiveness ratios (ICERs) for PET/MRI were calculated. RESULTS: Two hundred sixty-three patients (330 same-day PET/CT and PET/MRI examinations) were included. PET/MRI was accurate in 319/330 examinations and PET/CT in 277/330 examinations; the respective accuracies of 97.3% and 83.9% differed significantly (P < 0.001). The additional findings on PET/MRI-mainly liver and brain metastases-had implications for patient management in 21/263 patients (8.0%). The per-examination cost was 596.97 EUR for PET/MRI and 405.95 EUR for PET/CT. ICERs for PET/MRI were 14.26 EUR per percent of diagnostic accuracy and 23.88 EUR per percent of correctly managed patients. CONCLUSIONS: PET/MRI enables more appropriate management than PET/CT in a nonnegligible fraction of cancer patients. Since the per-examination cost is about 50% higher for PET/MRI than for PET/CT, a histology-based triage of patients to either PET/MRI or PET/CT may be meaningful.

RECIL versus Lugano for Treatment Response Assessment in FDG-Avid Non-Hodgkin Lymphomas: A Head-to-Head Comparison in 54 Patients.

The response evaluation criteria in lymphoma (RECIL) classification for lymphoma treatment response assessment was introduced in 2017, but it has not yet been compared to the established Lugano classification. Also, the value of the provisional "minor response" (MiR) category of RECIL is unclear. In 54 patients with FDG-avid non-Hodgkin lymphomas (41 diffuse large B-cell lymphomas (DLBCL) and 13 follicular lymphomas), [18F]FDG-PET/CT-based response according to RECIL and Lugano was determined at interim and end-of-treatment (EOT) restaging. Rates of agreement and Cohen's kappa (κ) coefficients were calculated. The relationship between RECIL and Lugano responses and 2-year complete remission (CR) status of DLBCL patients was determined. At interim restaging, MiR was observed in 14.8%, and at EOT, in 5.6% of patients. When MiR was recoded as partial remission, agreement between RECIL and Lugano was 83.3% at interim restaging (κ = 0.69), and 90.7% at EOT (κ = 0.79). 85.4%, of DLBCL patients with responding disease at interim restaging according to both RECIL and Lugano achieved 2-year CR status; whereas, at EOT, 82.9% of patients with responding disease according to Lugano, and 85.4% of patients with responding disease according to RECIL, achieved 2-year CR status. Thus, RECIL and Lugano classifications show comparable performance for treatment response assessment, and a similar association with 2-year CR status in FDG-avid lymphomas.

Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer.

PURPOSE: The first aim of this study was to evaluate 68Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA PET) parameters for assessment of response to 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). The second aim was to investigate factors associated with overall survival (OS). METHODS: We retrospectively assessed mean standardized uptake values (SUVmean) and total tumor volumes (TTV) on PSMA PET in 38 of 55 mCRPC patients before and after RLT. PSA testing and PSMA PET/CT(MRI) imaging were performed during the 8 weeks before and the 6 weeks after RLT. PSMA PET and CT(MRI) images were reviewed separately according to the modified PET Response Criteria in Solid Tumors (mPERCIST) and RECIST1.1. The results were compared with PSA responses. Associations between OS and the RECIST evaluation and changes in SUVmean, TTV, and PSA, CRP, LDH, hemoglobin and ALP levels were determined in a univariable survival analysis. RESULTS: The median PSA level at the time of pretherapy PSMA PET/CT(MRI) was 60.8 ng/ml (IQR 15.4, 264.2 ng/ml). After RLT the median PSA level decreased by 44%, TTV by 45.1%, SUVmean by 25.8% and RECIST by 11.3%. A PSA response was seen in 18 patients (47.4%), stable disease in 12 (31.6%) and progressive disease in 8 (21.1%). Contrary to the changes in SUVmean and the RECIST evaluation, the change in TTV was significantly associated with PSA response (p = 0.15, p = 0.58, and p < 0.001, respectively). After a median follow-up of 17 months (IQR 8.0, 24.2 months), 11 patients (28.9%) had died of their prostate cancer. The changes in both TTV and PSA levels were associated with OS (HR 1.001, 95% CI 1-1.003, p = 0.04, and HR 1.004, 95% CI 1.001-1.008, p = 0.01, respectively), while the changes in SUVmean and the RECIST evaluation were not. The pre-therapy CRP level was also associated with OS (HR 1.07, 95% CI 1.009-1.14, p = 0.02). CONCLUSION: TTV on PSMA PET seems to be a reliable parameter for response assessment in mCRPC patients undergoing RLT and might overcome the limitations of RECIST in prostate cancer. Furthermore, the change in TTV was significantly associated with OS in our cohort.

Ultra-early response assessment in lymphoma treatment: [18F]FDG PET/MR captures changes in glucose metabolism and cell density within the first 72 hours of treatment.

PURPOSE: To determine whether, in patients with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL), [18F]FDG PET/MR can capture treatment effects within the first week after treatment initiation, and whether changes in glucose metabolism and cell density occur simultaneously. METHODS: Patients with histologically proven HL or NHL were included in this prospective IRB-approved study. Patients underwent [18F]FDG PET/MR before, and then 48-72 h after (follow-up 1, FU-1) and 1 week after (FU-2) initiation of the first cycle of their respective standard chemotherapy (for HL) or immunochemotherapy (for NHL). Standardized [18F]FDG uptake values (SUVmax, SUVmean) and apparent diffusion coefficients (ADCmin, ADCmean) based on diffusion-weighted MRI, and metabolic and morphological tumour volumes (MTV, VOL) were assessed at each time-point. Multilevel analyses with an unstructured covariance matrix, and pair-wise post-hoc tests were used to test for significant changes in SUVs, ADCs, MTVs and VOLs between the three time-points. RESULTS: A total of 58 patients (11 with HL and 47 with NHL) with 166 lesions were analysed. Lesion-based mean rates of change in SUVmax, SUVmean, ADCmin, ADCmean, MTV and VOL between baseline and FU-1 were -46.8%, -33.3%, +20.3%, +14%, -46% and -12.8%, respectively, and between baseline and FU-2 were -65.1%, -49%, +50.7%, +32.4%, -61.1% and -24.2%, respectively. These changes were statistically significant (P < 0.01) except for the change in VOL between baseline and FU-1 (P = 0.079). CONCLUSION: In lymphoma patients, [18F]FDG PET/MR can capture treatment-induced changes in glucose metabolism and cell density as early as 48-72 h after treatment initiation.

Quantitative assessment of atherosclerotic plaques on (18)F-FDG PET/MRI: comparison with a PET/CT hybrid system.

PURPOSE: PET with (18)F-FDG has the potential to assess vascular macrophage metabolism. (18)F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel (18)F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of (18)F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques. METHODS: The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with (18)F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUVmax) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated. RESULTS: Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUVmax values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3 ± 0.6 vs. 3.1 ± 0.6; P < 0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman's r = 0.67, P < 0.01). In contrast, TBRmax values of plaque lesions were similar on PET/MRI and on PET/CT (2.2 ± 0.3 vs. 2.2 ± 0.3; P = 0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman's r = 0.73, P < 0.01). Considering the increasing trend in SUVmax and TBRmax values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBRmax values may also be expected with PET/MRI compared with PET/CT. CONCLUSION: SUVmax and TBRmax values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUVmax and TBRmax with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI.