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Journal of Nuclear Medicine : Official... Mar 2015SPECT with submegabecquerel amounts of tracer or subsecond time resolution would enable a wide range of new imaging protocols such as screening tracers with initially...
UNLABELLED
SPECT with submegabecquerel amounts of tracer or subsecond time resolution would enable a wide range of new imaging protocols such as screening tracers with initially low yield or labeling efficiency, imaging low receptor densities, or even performing SPECT outside regular radiation laboratories. To this end we developed dedicated ultra-high-sensitivity pinhole SPECT.
METHODS
A cylindric collimator with 54 focused 2.0-mm-diameter conical pinholes was manufactured and mounted in a stationary small-animal SPECT system. The system matrix for image reconstruction was calculated via a hybrid method based on both (99m)Tc point source measurements and ray-tracing analytic modeling. SPECT images were reconstructed using pixel-based ordered-subsets expectation maximization. Performance was evaluated with phantoms and low-dose bone, dynamic kidney, and cardiac mouse scans.
RESULTS
The peak sensitivity reached 1.3% (13,080 cps/MBq). The reconstructed spatial resolution (rod visibility in a micro-Jaszczak phantom) was 0.85 mm. Even with only a quarter megabecquerel of activity, 30-min bone SPECT scans provided surprisingly high levels of detail. Dynamic dual-isotope kidney and (99m)Tc-sestamibi cardiac scans were acquired with a time-frame resolution down to 1 s.
CONCLUSION
The high sensitivity achieved increases the range of mouse SPECT applications by enabling in vivo imaging with less than a megabecquerel of tracer activity or down to 1-s frame dynamics.
Topics: Animals; Bone and Bones; Calibration; Equipment Design; Heart; Image Processing, Computer-Assisted; Kidney; Mice; Mice, Inbred C57BL; Phantoms, Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Technetium; Technetium Tc 99m Sestamibi; Time Factors; Tomography, Emission-Computed, Single-Photon
PubMed: 25678487
DOI: 10.2967/jnumed.114.147140 -
Molecular Pharmaceutics Jan 2019Antibody fragment F8-mediated interleukin 10 (IL10) delivery is a novel treatment for rheumatoid arthritis (RA). F8 binds to the extra-domain-A of fibronectin (ED-A). In...
Antibody fragment F8-mediated interleukin 10 (IL10) delivery is a novel treatment for rheumatoid arthritis (RA). F8 binds to the extra-domain-A of fibronectin (ED-A). In this study, in vivo biodistribution and arthritis targeting of radiolabeled F8-IL10 were investigated in RA patients, followed by further animal studies. Therefore, three RA patients (DAS28 > 3.2) received 0.4 mg of 30-74 megabecquerel [I]I-F8-IL10 for PET-CT and blood sampling. In visually identified PET-positive joints, target-to-background was calculated. Healthy mice, rats, and arthritic rats were injected with iodinated F8-IL10 or KSF-IL10 control antibody. Various organs were excised, weighed, and counted for radioactivity. Tissue sections were stained for fibronectin ED-A. In RA patients, [I]I-F8-IL10 was cleared rapidly from the circulation with less than 1% present in blood after 5 min. PET-CT showed targeting in 38 joints (11-15 per patient) and high uptake in the liver and spleen. Mean target-to-background ratios of PET-positive joints were 2.5 ± 1.2, 1.5 times higher for clinically active than clinically silent joints. Biodistribution of radioiodinated F8-IL10 in healthy mice showed no effect of the radioiodination method. [I]I-F8-IL10 joint uptake was also demonstrated in arthritic rats, ∼14-fold higher than that of the control antibody [I]I-KSF-IL10 ( p < 0.001). Interestingly, liver and spleen uptake were twice as high in arthritic than in healthy rats and were related to increased (∼7×) fibronectin ED-A expression in these tissues. In conclusion, [I]I-F8-IL10 uptake was observed in arthritic joints in RA patients holding promise for visualization of inflamed joints by PET-CT imaging and therapeutic targeting. Patient observations and, subsequently, arthritic animal studies pointed to awareness of increased [I]I-F8-IL10 uptake in the liver and spleen associated with moderate systemic inflammation. This translational study demonstrated the value of in vivo biodistribution and PET-CT-guided imaging in development of new and potential antirheumatic drugs'.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Interleukin-10; Liver; Male; Mice; Positron-Emission Tomography; Rats; Spleen
PubMed: 30550295
DOI: 10.1021/acs.molpharmaceut.8b00982 -
European Radiology Oct 2023To assess the evolution of administered radiotracer activity for F-18-fluorodeoxyglucose (18F-FDG) PET/CT or PET/MR in pediatric patients (0-16 years) between years 2000...
OBJECTIVES
To assess the evolution of administered radiotracer activity for F-18-fluorodeoxyglucose (18F-FDG) PET/CT or PET/MR in pediatric patients (0-16 years) between years 2000 and 2021.
METHODS
Pediatric patients (≤ 16 years) referred for 18F-FDG PET/CT or PET/MR imaging of the body during 2000 and 2021 were retrospectively included. The amount of administered radiotracer activity in megabecquerel (MBq) was recorded, and signal-to-noise ratio (SNR) was measured in the right liver lobe with a 4 cm volume of interest as an indicator for objective image quality. Descriptive statistics were computed.
RESULTS
Two hundred forty-three children and adolescents underwent a total of 466 examinations. The median injected 18F-FDG activity in MBq decreased significantly from 296 MBq in 2000-2005 to 100 MBq in 2016-2021 (p < 0.001), equaling approximately one-third of the initial amount. The median SNR ratio was stable during all years with 11.7 (interquartile range [IQR] 10.7-12.9, p = 0.133).
CONCLUSIONS
Children have benefited from a massive reduction in the administered 18F-FDG dose over the past 20 years without compromising objective image quality.
CLINICAL RELEVANCE STATEMENT
Radiotracer dose was reduced considerably over the past two decades of pediatric F-18-fluorodeoxyglucose PET/CT and PET/MR imaging highlighting the success of technical innovations in pediatric PET imaging.
KEY POINTS
• The evolution of administered radiotracer activity for F-18-fluorodeoxyglucose (18F-FDG) PET/CT or PET/MR in pediatric patients (0-16 years) between 2000 and 2021 was assessed. • The injected tracer activity decreased by 66% during the study period from 296 megabecquerel (MBq) to 100 MBq (p < 0.001). • The continuous implementation of technical innovations in pediatric hybrid 18F-FDG PET has led to a steady decrease in the amount of applied radiotracer, which is particularly beneficial for children who are more sensitive to radiation.
PubMed: 37855853
DOI: 10.1007/s00330-023-10319-6 -
Clinical Drug Investigation Jan 2022BACKGROUND AND OBJECTIVES: BI 425809, a novel glycine transporter-1 inhibitor, may ameliorate cognitive deficits in schizophrenia. The objectives of the studies were:...
The Absolute Bioavailability, Absorption, Distribution, Metabolism, and Excretion of BI 425809 Administered as an Oral Dose or an Oral Dose with an Intravenous Microtracer Dose of [C]-BI 425809 in Healthy Males.
UNLABELLED
BACKGROUND AND OBJECTIVES: BI 425809, a novel glycine transporter-1 inhibitor, may ameliorate cognitive deficits in schizophrenia. The objectives of the studies were: to assess absolute bioavailability of oral BI 425809 compared with intravenous (IV) microtracer infusion (study 1), and to determine the mass balance, distribution, metabolism, and excretion of BI 425809 (study 2).
METHODS
These were Phase I, open-label, non-randomized, single-period, single-arm studies in healthy males. Study 1 administered a single oral dose of unlabeled BI 425809 25 mg, then an IV microtracer infusion of [C]-BI 425809 30 µg. In study 2, participants received an oral dose of [C]-BI 425809 25 mg containing [C]-labeled (dose: 3.7 megabecquerel (0.41 mSv)) and unlabeled drug. Safety was assessed.
RESULTS
In study 1 (n = 6), the absolute bioavailability of a 25 mg tablet of BI 425809 in a fasted state was 71.64%. The geometric mean dose-normalized maximum plasma concentration was approximately 80% lower after oral administration versus IV dose. In study 2 (n = 6), the total recovery of [C]-BI 425809 was 96.7%, with ~ 48% of [C]-radioactivity excreted in urine and ~ 48% excreted in feces. Among the labeled drug in urine, ~ 45% of the amount excreted was composed of BI 425809 (17.4%) and two metabolites (BI 758790, 21.0%; BI 761036, 5.9%). In feces, < 1% of BI 425809 was excreted as unchanged drug. In both studies, BI 425809 was generally well tolerated.
CONCLUSIONS
After normalization, the absolute bioavailability of tablet-form BI 425809 was 71.64%. The total recovery of [C]-BI 425809 25 mg was high (96.7%), with low intraindividual variability and similar amounts excreted in urine and feces. CLINICALTRIALS.
GOV IDENTIFIERS
NCT03783000 and NCT03654170.
Topics: Administration, Intravenous; Administration, Oral; Biological Availability; Humans; Male; Organic Chemicals
PubMed: 34936055
DOI: 10.1007/s40261-021-01111-9 -
World Journal of Nuclear Medicine 2019We compared preoperative regular activity and low-activity radiology-based predictions with real surgical and pathological findings for parathyroidectomy surgery. The...
We compared preoperative regular activity and low-activity radiology-based predictions with real surgical and pathological findings for parathyroidectomy surgery. The study retrospectively analyzed 54 consecutive cases (2009-2016) for benign tumor removal. Technetium-99m (Tc-99m)-sestamibi was used as a diagnostic radiopharmaceutical for diagnostic dual-phase parathyroid scintigraphy and single-photon emission computed tomography/computed tomography. We assessed images obtained with the radiation activity of 925 megabecquerel (MBq) and images obtained with the activity of 185 MBq. The study compared preoperative evaluation of tumor presence, multiplicity, location, and the type of pathology with actual data that were revealed during the operation and pathological investigation. The agreement between preoperative radiological prediction and actual location, number, and type of the parathyroid lesions was achieved in 98.4% ( = 61/62 lesions). The agreement between 925 MBq-based and 185-MBq based investigations was 100%. The agreement between radiological and pathological findings was 100% for both investigations. Our data suggest that the radioactivity of 185 MBq applied in the evaluation of the parathyroid glands provides results similar to the currently used 925-1110 MBq if used for diagnostic dual-phase parathyroid scintigraphy with Tc-99m-sestamibi. Such radioactivity may reduce the exposure to radiation of the patients and the staff without compromising results of the investigation.
PubMed: 30774547
DOI: 10.4103/wjnm.WJNM_29_18 -
Medicine Oct 2014The aim of this article is to investigate the cortical metabolic arrangements in olfactory processing by using F fluorodeoxyglucose (FDG) positron emission...
The aim of this article is to investigate the cortical metabolic arrangements in olfactory processing by using F fluorodeoxyglucose (FDG) positron emission tomography/computed tomography.Twenty-six normosmic individuals (14 women and 12 men; mean age 46.7 ± 10 years) were exposed to a neutral olfactory condition (NC) and, after 1 month, to a pure olfactory condition (OC) in a relatively ecological environment, that is, outside the scanner. All the subjects were injected with 185-210 megabecquerel of F FDG during both stimulations. Statistical parametric mapping version 2 was used in order to assess differences between NC and OC.As a result, we found a significant higher glucose consumption during OC in the cuneus, lingual, and parahippocampal gyri, mainly in the left hemisphere. During NC, our results show a relative higher glucose metabolism in the left superior, inferior, middle, medial frontal, and orbital gyri as well as in the anterior cingulate cortex.The present investigation, performed with a widely available functional imaging clinical tool, may help to better understand the neural responses associated to olfactory processing in healthy individuals and in patients with olfactory disorders by acquiring data in an ecologic, noise-free, and resting condition in which possible cerebral activations related to unwanted attentional processes might be avoided.
Topics: Adult; Brain Mapping; Cerebral Cortex; Female; Fluorodeoxyglucose F18; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Olfactory Pathways; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed
PubMed: 25340494
DOI: 10.1097/MD.0000000000000103