scholarly journals Human Biodistribution and Radiation Dosimetry of the P-Glycoprotein Radiotracer [11C]Metoclopramide

Author(s):  
Martin Bauer ◽  
Sandra Barna ◽  
Matthias Blaickner ◽  
Konstantin Prosenz ◽  
Karsten Bamminger ◽  
...  

Abstract Purpose To assess in healthy volunteers the whole-body distribution and dosimetry of [11C]metoclopramide, a new positron emission tomography (PET) tracer to measure P-glycoprotein activity at the blood-brain barrier. Procedures Ten healthy volunteers (five women, five men) were intravenously injected with 387 ± 49 MBq of [11C]metoclopramide after low dose CT scans and were then imaged by whole-body PET scans from head to upper thigh over approximately 70 min. Ten source organs (brain, thyroid gland, right lung, myocardium, liver, gall bladder, left kidney, red bone marrow, muscle and the contents of the urinary bladder) were manually delineated on whole-body images. Absorbed doses were calculated with QDOSE (ABX-CRO) using the integrated IDAC-Dose 2.1 module. Results The majority of the administered dose of [11C]metoclopramide was taken up into the liver followed by urinary excretion and, to a smaller extent, biliary excretion of radioactivity. The mean effective dose of [11C]metoclopramide was 1.69 ± 0.26 μSv/MBq for female subjects and 1.55 ± 0.07 μSv/MBq for male subjects. The two organs receiving the highest radiation doses were the urinary bladder (10.81 ± 0.23 μGy/MBq and 8.78 ± 0.89 μGy/MBq) and the liver (6.80 ± 0.78 μGy/MBq and 4.91 ± 0.74 μGy/MBq) for female and male subjects, respectively. Conclusions [11C]Metoclopramide showed predominantly renal excretion, and is safe and well tolerated in healthy adults. The effective dose of [11C]metoclopramide was comparable to other 11C-labeled PET tracers.

2011 ◽  
Vol 11 (Suppl 2) ◽  
pp. A46
Author(s):  
Martin Bauer ◽  
Markus Zeitlinger ◽  
Georg Dobrozemsky ◽  
Cécile Philippe ◽  
Markus Müller ◽  
...  

2020 ◽  
Vol 47 (11) ◽  
pp. 2549-2561 ◽  
Author(s):  
Suraiya R. Dubash ◽  
Nicholas Keat ◽  
Kasia Kozlowski ◽  
Chris Barnes ◽  
Louis Allott ◽  
...  

Abstract Background Fatty acids derived de novo or taken up from the extracellular space are an essential source of nutrient for cell growth and proliferation. Radiopharmaceuticals including 11C-acetate, and 18F-FAC (2-18F-fluoroacetate), have previously been used to study short-chain fatty acid (SCFA) metabolism. We developed 18F-fluoropivalate (18F-FPIA; 3-18F-fluoro-2,2-dimethylpropionic acid) bearing a gem-dimethyl substituent to assert metabolic stability for studying SCFA metabolism. We report the safety, biodistribution, and internal radiation dosimetry profile of 18F-FPIA in 24 healthy volunteers and the effect of dietary conditions. Materials and methods Healthy volunteer male and female subjects were enrolled (n = 24), and grouped into 12 fed and 12 fasted. Non-esterified fatty acids (NEFA) and carnitine blood measurements were assessed. Subjects received 159.48 MBq (range, 47.31–164.66 MBq) of 18F-FPIA. Radiochemical purity was > 99%. Safety data were obtained during and 24 h after radiotracer administration. Subjects underwent detailed multiple whole-body PET/CT scanning with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated using OLINDA 1.1. Results All subjects tolerated 18F-FPIA with no adverse events. Over 90% of radiotracer was present in plasma at 60 min post-injection. The organs receiving highest absorbed dose (in mGy/MBq) were the liver (0.070 ± 0.023), kidneys (0.043 ± 0.013), gallbladder wall (0.026 ± 0.003), and urinary bladder (0.021 ± 0.004); otherwise there was low tissue uptake. The calculated effective dose using mean organ residence times over all 24 subjects was 0.0154 mSv/MBq (SD ± 0.0010). No differences in biodistribution or dosimetry were seen in fed and fasted subjects, though systemic NEFA and carnitine levels reflected fasted and fed states. Conclusion The favourable safety, imaging, and dosimetric profile makes 18F-FPIA a promising candidate radiotracer for tracing SCFA metabolism.


2007 ◽  
Vol 34 (4) ◽  
pp. 465-470 ◽  
Author(s):  
Maria-João Ribeiro ◽  
Marcel Ricard ◽  
Marie-Angele Lièvre ◽  
Sandrine Bourgeois ◽  
Patrick Emond ◽  
...  

2002 ◽  
Vol 41 (02) ◽  
pp. 102-107 ◽  
Author(s):  
J. Kopp ◽  
H. Vogt ◽  
F. Wawroschek ◽  
S. Gröber ◽  
R. Dorn ◽  
...  

Summary Aim: To visualise the sentinel lymph nodes (SLNs) of the prostate we injected the radiotracer into the parenchyma of the prostate. The activity was deposited in liver, spleen, bone marrow, urinary bladder and regional lymphatic system. The aim of this work is to determine biokinetical data and to estimate radiation doses to the patient. Methods: The patients with prostate cancer received a sonographically controlled, transrectal administration of 99mTc-Nanocoll®, injected directly into both prostate lobes. In 10 randomly selected patients radionuclide distribution and its time course was determined via regions of interest (ROIs) over prostate, urinary bladder, liver, spleen and the lymph nodes. The uptake in the SLNs was estimated from gamma probe measurements at the surgically removed nodes. To compare tumour positive with tumour free lymph nodes according to SLN-uptake and SLNlocalisation we evaluated 108 lymph nodes out of 24 patients with tumour positive SLN. For calculating the effective dose according to ICRP 60 of the patients we used the MIRD-method and the Mirdose 3.1 software. Results: The average uptake of separate organs was: bladder content 24%, liver 25.5%, spleen 2%, sum of SLN 0.5%. An average of 9% of the applied activity remained in the prostate. The residual activity was mainly accumulated in bone marrow and blood. Occasionally a weak activity enrichment in intestinal tract and kidneys could be recognized. The effective dose to the patient was estimated to 7.6 μSv/MBq. The radioactivity uptake of the SLN varied in several orders of magnitude between 0.006% and 0.6%. The probability of SLN-metastasis was found to be independent from tracer uptake in the lymph node. The radioactivity uptake of the SLNs in distinct lymph node regions showed no significant differences. Conclusion: The radiotracer is transferred out of the prostate via blood flow, by direct transfer via the urethra into the bladder and by lymphatic transport. Injecting a total activity of 200 MBq leads to a mean effective dose of 1.5 mSv. It is not recommended to use the tracer uptake in lymph nodes as the only criterion to characterize SLNs.


Dose-Response ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 155932582097313
Author(s):  
Dario Baldi ◽  
Liberatore Tramontano ◽  
Vincenzo Alfano ◽  
Bruna Punzo ◽  
Carlo Cavaliere ◽  
...  

For decades, the main imaging tool for multiple myeloma (MM) patient’s management has been the conventional skeleton survey. In 2014 international myeloma working group defined the advantages of the whole-body low dose computed tomography (WBLDCT) as a gold standard, among imaging modalities, for bone disease assessment and subsequently implemented this technique in the MM diagnostic workflow. The aim of this study is to investigate, in a group of 30 patients with a new diagnosis of MM, the radiation dose (CT dose index, dose-length product, effective dose), the subjective image quality score and osseous/extra-osseous findings rate with a modified WBLDCT protocol. Spectral shaping and third-generation dual-source multidetector CT scanner was used for the assessment of osteolytic lesions due to MM, and the dose exposure was compared with the literature findings reported until 2020. Mean radiation dose parameters were reported as follows: CT dose index 0.3 ± 0.1 mGy, Dose-Length Product 52.0 ± 22.5 mGy*cm, effective dose 0.44 ± 0.19 mSv. Subjective image quality was good/excellent in all subjects. 11/30 patients showed osteolytic lesions, with a percentage of extra-osseous findings detected in 9/30 patients. Our data confirmed the advantages of WBLDCT in the diagnosis of patients with MM, reporting an effective dose for our protocol as the lowest among previous literature findings.


2021 ◽  
Vol 34 (1) ◽  
pp. 124-133
Author(s):  
David J. Winkel ◽  
Hanns-Christian Breit ◽  
Thomas J. Weikert ◽  
Bram Stieltjes

AbstractTo explore the feasibility of a fully automated workflow for whole-body volumetric analyses based on deep reinforcement learning (DRL) and to investigate the influence of contrast-phase (CP) and slice thickness (ST) on the calculated organ volume. This retrospective study included 431 multiphasic CT datasets—including three CP and two ST reconstructions for abdominal organs—totaling 10,508 organ volumes (10,344 abdominal organ volumes: liver, spleen, and kidneys, 164 lung volumes). Whole-body organ volumes were determined using multi-scale DRL for 3D anatomical landmark detection and 3D organ segmentation. Total processing time for all volumes and mean calculation time per case were recorded. Repeated measures analyses of variance (ANOVA) were conducted to test for robustness considering CP and ST. The algorithm calculated organ volumes for the liver, spleen, and right and left kidney (mean volumes in milliliter (interquartile range), portal venous CP, 5 mm ST: 1868.6 (1426.9, 2157.8), 350.19 (45.46, 395.26), 186.30 (147.05, 214.99) and 181.91 (143.22, 210.35), respectively), and for the right and left lung (2363.1 (1746.3, 2851.3) and 1950.9 (1335.2, 2414.2)). We found no statistically significant effects of the variable contrast phase or the variable slice thickness on the organ volumes. Mean computational time per case was 10 seconds. The evaluated approach, using state-of-the art DRL, enables a fast processing of substantial amounts irrespective of CP and ST, allowing building up organ-specific volumetric databases. The thus derived volumes may serve as reference for quantitative imaging follow-up.


2009 ◽  
Vol 297 (1) ◽  
pp. E134-E141 ◽  
Author(s):  
Ichiro Sakata ◽  
Jing Yang ◽  
Charlotte E. Lee ◽  
Sherri Osborne-Lawrence ◽  
Sherry A. Rovinsky ◽  
...  

Ghrelin is a peptide hormone with many known functions, including orexigenic, blood glucose-regulatory, and antidepressant actions, among others. Mature ghrelin is unique in that it is the only known naturally occurring peptide to be posttranslationally modified by O-acylation with octanoate. This acylation is required for many of ghrelin's actions, including its effects on promoting increases in food intake and body weight. GOAT (ghrelin O-acyltransferase), one of 16 members of the MBOAT family of membrane-bound O-acyltransferases, has recently been identified as the enzyme responsible for catalyzing the addition of the octanoyl group to ghrelin. Although the initial reports of GOAT have localized its encoding mRNA to tissues known to contain ghrelin, it is as yet unclear whether the octanoylation occurs within ghrelin-producing cells or in neighboring cells. Here, we have performed dual-label histochemical analysis on mouse stomach sections and quantitative PCR on mRNAs from highly enriched pools of mouse gastric ghrelin cells to demonstrate a high degree of GOAT mRNA expression within ghrelin-producing cells of the gastric oxyntic mucosa. We also demonstrate that GOAT is the only member of the MBOAT family whose expression is highly enriched within gastric ghrelin cells and whose whole body distribution mirrors that of ghrelin.


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