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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 -
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 -
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 -
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 -
Journal of Nuclear Medicine Technology Mar 2014Combined PET and SPECT scanning can give supplementary information. However, activity from PET radionuclides can cause background counts and increased dead time in γ...
UNLABELLED
Combined PET and SPECT scanning can give supplementary information. However, activity from PET radionuclides can cause background counts and increased dead time in γ camera imaging (SPECT or planar) because the 511-keV photons can penetrate collimators designed for lower energies. This study investigated how to manage this issue, including what levels of PET radionuclides can be tolerated when a γ-camera investigation is performed.
METHODS
Different combinations of (68)Ga (PET radionuclide), (99m)Tc (low-energy radionuclide), and (111)In (medium-energy radionuclide) were scanned by a γ camera. Standard low-, medium-, and high-energy collimators were used with the γ camera. Dead time and counts near and distant from the sources were recorded.
RESULTS
Down scatter from 511 keV can give rise to a considerable number of counts within the (99m)Tc or (111)In energy windows, especially when the PET source is close to the camera head. Over the full camera head, the PET source can result in more counts per megabecquerel than the SPECT source ((99m)Tc or (111)In). Counts from the PET source were distributed over a large region of the camera head. With medium- and high-energy collimators, the sensitivity to the PET radionuclide was found to be about 10% of the sensitivity to (99m)Tc and about 20% of the sensitivity to (111)In, as measured within a 3-cm-radius region of interest.
CONCLUSION
If PET radionuclides of activity 1 MBq or higher are present in the patient at the time of SPECT, a medium-energy collimator should be used. Counts from PET sources will in SPECT usually be seen as a diffuse background rather than as foci. The thick septa of high-energy collimators may result in structure in the image, and a high-energy collimator is recommended only if PET activity is greater than 10 MBq.
Topics: Half-Life; Positron-Emission Tomography; Reference Standards; Tomography, Emission-Computed, Single-Photon
PubMed: 24470597
DOI: 10.2967/jnmt.113.131003 -
Small (Weinheim An Der Bergstrasse,... Aug 2011Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation...
Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation challenging. Therefore, a more suitable way to harness its attributes in a clinical setting would be to couple Raman spectroscopy with endoscopy. The use of an accessory Raman endoscope in conjunction with topically administered tumor-targeting Raman nanoparticles during a routine colonoscopy could offer a new way to sensitively detect dysplastic lesions while circumventing Raman's limited depth of penetration and avoiding systemic toxicity. In this study, the natural biodistribution of gold surface-enhanced Raman scattering (SERS) nanoparticles is evaluated by radiolabeling them with (64) Cu and imaging their localization over time using micropositron emission tomography (PET). Mice are injected either intravenously (IV) or intrarectally (IR) with approximately 100 microcuries (μCi) (3.7 megabecquerel (MBq)) of (64) Cu-SERS nanoparticles and imaged with microPET at various time points post injection. Quantitative biodistribution data are obtained as % injected dose per gram (%ID g(-1)) from each organ, and the results correlate well with the corresponding microPET images, revealing that IV-injected mice have significantly higher uptake (p < 0.05) in the liver (5 h = 8.96% ID g(-1); 24 h = 8.27% ID g(-1)) than IR-injected mice (5 h = 0.09% ID g(-1); 24 h = 0.08% ID g(-1)). IR-injected mice show localized uptake in the large intestine (5 h = 10.37% ID g(-1); 24 h = 0.42% ID g(-1)) with minimal uptake in other organs. Raman imaging of excised tissues correlate well with biodistribution data. These results suggest that the topical application of SERS nanoparticles in the mouse colon appears to minimize their systemic distribution, thus avoiding potential toxicity and supporting the clinical translation of Raman spectroscopy as an endoscopic imaging tool.
Topics: Animals; Copper Radioisotopes; Endoscopy; Female; Mice; Mice, Nude; Microscopy, Electron, Transmission; Nanoparticles; Positron-Emission Tomography; Spectrum Analysis, Raman
PubMed: 21608124
DOI: 10.1002/smll.201002317 -
Molecular Therapy : the Journal of the... Apr 2011We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of radioiodine in neuroblastoma tumors after systemic nonviral polyplex-mediated sodium...
We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of radioiodine in neuroblastoma tumors after systemic nonviral polyplex-mediated sodium iodide symporter (NIS) gene delivery. In the present study, we used novel polyplexes based on linear polyethylenimine (LPEI), polyethylene glycol (PEG), and the synthetic peptide GE11 as an epidermal growth factor receptor (EGFR)-specific ligand to target a NIS-expressing plasmid to hepatocellular carcinoma (HCC) (HuH7). Incubation of HuH7 cells with LPEI-PEG-GE11/NIS polyplexes resulted in a 22-fold increase in iodide uptake, which was confirmed in other cancer cell lines correlating well with EGFR expression levels. Using (123)I-scintigraphy and ex vivo γ-counting, HuH7 xenografts accumulated 6.5-9% injected dose per gram (ID/g) (123)I, resulting in a tumor-absorbed dose of 47 mGray/Megabecquerel (mGy/MBq) (131)Iodide ((131)I) after intravenous (i.v.) application of LPEI-PEG-GE11/NIS. No iodide uptake was observed in other tissues. After pretreatment with the EGFR-specific antibody cetuximab, tumoral iodide uptake was markedly reduced confirming the specificity of EGFR-targeted polyplexes. After three or four cycles of polyplex/(131)I application, a significant delay in tumor growth was observed associated with prolonged survival. These results demonstrate that systemic NIS gene transfer using polyplexes coupled with an EGFR-targeting ligand is capable of inducing tumor-specific iodide uptake, which represents a promising innovative strategy for systemic NIS gene therapy in metastatic cancers.
Topics: Cell Line, Tumor; ErbB Receptors; Genetic Therapy; Humans; Iodine Radioisotopes; Liver Neoplasms; Polyethylene Glycols; Polyethyleneimine; Polymerase Chain Reaction; Polymers; Symporters
PubMed: 21245850
DOI: 10.1038/mt.2010.296 -
Journal of Nuclear Medicine : Official... Dec 2010Current SPECT radioligands available for in vivo imaging of the dopamine transporter (DAT) also show affinity for monoamine transporters other than DAT, especially the... (Comparative Study)
Comparative Study Randomized Controlled Trial
UNLABELLED
Current SPECT radioligands available for in vivo imaging of the dopamine transporter (DAT) also show affinity for monoamine transporters other than DAT, especially the serotonin transporter (SERT). The effect of this lack of selectivity for in vivo imaging is unknown. In this study, we compared the SPECT radioligands (123)I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ((123)I-FP-CIT) and (123)I-N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl) nortropane ((123)I-PE2I), which has a 10-fold higher selectivity than (123)I-FP-CIT for DAT versus SERT [corrected].
METHODS
Sixteen healthy individuals were scanned in random order with both radioligands. The radioligands were administered according to standard recommendations: (123)I-FP-CIT was given as a bolus injection, and the ratio between the striatum and reference tissue was measured after 3 h. (123)I-PE2I was administered in a bolus-infusion setup, and the nondisplaceable binding potential (BP(ND)) was measured after 2 h. To assess the contribution of SERT to the overall SPECT signal, SERT was blocked by intravenous citalopram in 6 of the individuals.
RESULTS
The striatum-to-reference ratio - 1 of (123)I-FP-CIT was on average 18% higher than the striatal BP(ND) of (123)I-PE2I. Equal doses of radioactivity resulted in 3 times higher counting rates for (123)I-FP-CIT than for (123)I-PE2I, both in target and in reference brain regions. Citalopram infusion led to significant reductions in both striatal (22.8% ± 20.4%, P < 0.05) and thalamic (63.0% ± 47.9%, P < 0.05) (123)I-FP-CIT binding ratios, whereas BP(ND) of (123)I-PE2I was unaltered. Likewise, blocking of SERT led to increased (21% ± 30.1%, P < 0.001) plasma (123)I-FP-CIT, probably as a result of significant blocking of peripheral SERT binding sites. By contrast, plasma (123)I-PE2I remained stable.
CONCLUSION
(123)I-FP-CIT and (123)I-PE2I had approximately the same target-to-background ratios, but per injected megabecquerel, (123)I-FP-CIT gave rise to 3-fold higher cerebral counting rates. We found that (123)I-FP-CIT, but not (123)I-PE2I, brain images have a highly interindividual but significant signal contribution from SERT. Whether the SERT signal contribution is of clinical importance needs to be established in future patient studies.
Topics: Adult; Aged; Binding, Competitive; Brain; Citalopram; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Neostriatum; Nortropanes; Protein Binding; Radiopharmaceuticals; Scintillation Counting; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult
PubMed: 21078806
DOI: 10.2967/jnumed.110.078337