18F-sodium fluoride PET/MRI myocardial imaging in patients with suspected cardiac amyloidosis.

BACKGROUND: We evaluated the diagnostic performance of 18F-NaF PET/MRI in patients with suspected cardiac amyloidosis (CA). METHODS: Twenty-seven consecutive patients underwent myocardial PET 1 hour after injection of 4 MBq/kg 18F-NaF with simultaneous MRI including cine-MRI, T1 and T2 mapping, first-pass and late gadolinium enhancement (LGE). 18F-NaF uptake was measured visually and semi-quantitatively by calculating myocardium-to-blood pool (M/B) ratios. CA was confirmed histologically. RESULTS: Transthyretin (TTR)-CA was diagnosed in 16 patients, light-chain (AL)-CA in 7, and no-CA in 4. Visual interpretation of 18F-NaF images revealed a relative increase in myocardial uptake in only 3 patients, all with TTR CA, and a relative decrease in 13, including 7 AL CA, 3 no-CA, and 3 TTR CA. M/B ratios were significantly higher in TTR CA (1.00 ± 0.12) than in AL CA (0.81 ± 0.06, P = 0.001) or in no-CA (0.73 ± 0.16, P = 0.006). The optimal M/B cut-off to distinguish TTR CA from AL CA was ≥ 0.90 (Fischer, P = 0.0005). By comparison, classification of patients using 99mTc-HMDP heart-to-mediastinum ratios with the previously published cut-off ≥ 1.21 reached higher significance (P < 0.0001). Among MRI parameters, myocardial T1, LGE score, and extracellular volume were higher in CA than in no-CA patients, 1409 ± 76 vs 1278 ± 35 ms (P = 0.004), 10.35 ± 5.30 vs 3.50 ± 3.42 (P = 0.03), and 46 ± 10 vs 33 ± 8 % (P = 0.01), respectively. CONCLUSION: 18F-NaF PET/MRI shows good diagnostic performance when semi-quantification is used. However, contrast is low and visual interpretation may be challenging in routine. PET/MRI could constitute a one-stop-shop evaluation of amyloid load and cardiac function in patients needing rapid work-up.

Gated 18F-FDG PET/CT of the Lung Using a Respiratory Spirometric Gating Device: A Feasibility Study.

Spirometric gating devices (SGDs) can measure the respiratory signal with high temporal resolution and accuracy. The primary objective of this study was to assess the feasibility and tolerance of a gated lung PET/CT acquisition using an SGD. The secondary objective was to compare the technical quality, accuracy, and interoperability of the SGD with that of a standard respiratory gating device, Real-Time Position Management (RPM), based on measurement of vertical thoracoabdominal displacement. Methods: A prospective phase I monocentric clinical study was performed on patients undergoing 18F-FDG PET/CT for assessment of a solitary lung nodule, staging of lung malignancy, or planning of radiotherapy. After whole-body PET/CT, a centered gated acquisition of both PET and CT was simultaneously obtained with the SGD and RPM during normal breathing. Results: Of the 46 patients who were included, 6 were prematurely excluded (1 because of hyperglycemia and 5 because of distant metastases revealed by whole-body PET/CT, leading to an unjustified extra gated acquisition). No serious adverse events were observed. Of the 40 remaining patients, the gated acquisition was prematurely stopped in 1 patient because of mask discomfort (2.5%; confidence interval [CI], 0.1%-13.2%). This event was considered patient tolerance failure. The SGD generated accurately gated PET/CT images, with more than 95% of the breathing cycle detected and high temporal resolution, in 34 of the 39 patients (87.2%; 95% CI, 60.0%-100.0%) and failed to generate a biologic tumor volume in 1 of 21 patients with increased 18F-FDG uptake (4.8%; 95% CI, 0.1%-26.5%). The quality and accuracy of respiratory signal detection and synchronization were significantly better than those obtained with RPM (P < 0.05). Conclusion: This trial supports the use of an SGD for gated lung PET/CT because of its high patient tolerance and accuracy. Although this technique seems to technically outperform RPM for gated PET/CT, further assessment of its superiority and the clinical benefit is warranted. We believe that this technique could be used as a gold standard to develop innovative approaches to eliminate respiration-induced blurring artifacts.

Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma.

177Lu-DOTA-HH1 (177Lu-HH1) is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab) and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1) and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of 177Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg 177Lu-rituximab experienced severe radiation toxicity. The retention of 177Lu-rituximab in organs of the mononuclear phagocyte system was longer than for 177Lu-HH1, which explains the higher toxicity observed in mice treated with 177Lu-rituximab. In vitro internalization studies showed that 177Lu-HH1 internalizes faster and to a higher extent than 177Lu-rituximab which might be the reason for the better therapeutic effect of 177Lu-HH1.

Comparison of an alternative and existing binning methods to reduce the acquisition duration of 4D PET/CT.

PURPOSE: Respiratory motion is a source of artifacts that reduce image quality in PET. Four dimensional (4D) PET/CT is one approach to overcome this problem. Existing techniques to limiting the effects of respiratory motions are based on prospective phase binning which requires a long acquisition duration (15-25 min). This time is uncomfortable for the patients and limits the clinical exploitation of 4D PET/CT. In this work, the authors evaluated an existing method and an alternative retrospective binning method to reduce the acquisition duration of 4D PET/CT. METHODS: The authors studied an existing mixed-amplitude binning (MAB) method and an alternative binning method by mixed-phases (MPhB). Before implementing MPhB, they analyzed the regularity of the breathing patterns in patients. They studied the breathing signal drift and missing CT slices that could be challenging for implementing MAB. They compared the performance of MAB and MPhB with current binning methods to measure the maximum uptake, internal volume, and maximal range of tumor motion. RESULTS: MPhB can be implemented depending on an optimal phase (in average, the exhalation peak phase -4.1% of the entire breathing cycle duration). Signal drift of patients was in average 35% relative to the breathing amplitude. Even after correcting this drift, MAB was feasible in 4D CT for only 64% of patients. No significant differences appeared between the different binning methods to measure the maximum uptake, internal volume, and maximal range of tumor motion. The authors also determined the inaccuracies of MAB and MPhB to measure the maximum amplitude of tumor motion with three bins (less than 3 mm for movement inferior to 12 mm, up to 6.4 mm for a 21 mm movement). CONCLUSIONS: The authors proposed an alternative binning method by mixed-phase binning that halves the acquisition duration of 4D PET/CT. Mixed-amplitude binning was challenging because of signal drift and missing CT slices. They showed that more than three bins were necessary for a more accurate measurement of the maximum amplitude of the tumor motion. However, the current 4D-CT technology limits the increase of the number of bins in 4D PET/CT because of missing CT slices. One can reconstruct 4D PET images with more bins but without attenuation/scatter correction.

A new respiratory gating device to improve 4D PET/CT.

PURPOSE: Respiratory motion creates artifacts in positon emission tomography with computed tomography (PET/CT) images especially for lung tumors, and can alter diagnosis. To account for motion effects, respiratory gating techniques have been developed. However, the lack of measures strongly correlated with tumor motion limits their accuracy. The authors developed a real-time pneumotachograph device (SPI) allowing to sort PET and CT images depending on lung volumes. METHODS: The performance of this innovative respiratory tracking system was characterized and compared to a standard system. Our experimental setup consisted in a movable platform and a thorax phantom with six fillable spheres simulating lung tumors. The accuracy of SPI to detect inhalation peaks was also determined on volunteers. A comparison with the real-time position management (RPM) device, that relies on abdominal height measurement, was then investigated. RESULTS: Experiments showed a high accuracy of the measured signal compared to the input signal (R = 0.88 to 0.99), and of the detection of the inhalation peaks (error of 0.1 +/- 5.8 ms) necessary for prospective binning mode. Activity recovery coefficient was improved (until +39%) and the smearing effect was reduced (until 2.74 times lower) with SPI compared to ungated PET/CT acquisition. The spatial distribution of activity in spheres was similar for 4D PET gated with SPI and RPM. Significant improvement of the binning stability and matching between PET and CT were highlighted for irregular breathing patterns with SPI. CONCLUSIONS: SPI is an innovative device that provides better binning performance than the current gating device on phantom experiments. Future works will focus on patients where the authors expect a significant improvement of specificity and sensitivity of PET/CT examinations.

Efficacy of tiludronate in the treatment of horses with signs of pain associated with osteoarthritic lesions of the thoracolumbar vertebral column.

OBJECTIVE: To evaluate the efficacy of tiludronate for the treatment of horses with signs of pain associated with lesions of the thoracolumbar vertebral column. ANIMALS: 29 horses with clinical manifestations of pain associated with lesions of the thoracolumbar vertebral column and abnormal radiographic findings indicative of osteoarthritis of the articular processes-synovial intervertebral joints. PROCEDURES: Horses were initially examined in accordance with a standardized protocol, which included radiographic, ultrasonographic, and scintigraphic examinations. Fifteen horses were randomly assigned to receive tiludronate (1 mg/kg, IV, as a slow-rate infusion), and 14 horses received a control substance (day 0). Horses were monitored for the subsequent 120 days. Clinical evaluations were performed on days 60 and 120. Horses that had no evidence of clinical improvement on day 60 were administered tiludronate. Statistical analyses were performed to compare efficacy at day 60, improvement of dorsal flexibility at day 120, and dorsal flexibility before and 60 days after administration of tiludronate. RESULTS: Horses treated with tiludronate had significant improvement in dorsal flexibility between days 0 and 60, compared with control horses. Clinical improvement in dorsal flexibility was still evident at day 120. The percentage of positive responses was higher in the tiludronate group at 60 days. CONCLUSIONS AND CLINICAL RELEVANCE: Tiludronate had efficacy in the treatment of horses with signs of pain induced by osteoarticular lesions of the thoracolumbar vertebral column, causing a significant improvement in dorsal flexibility. Tiludronate may offer a treatment option for the management of horses with intervertebral lesions and the associated pain.