31 research outputs found
Comparison of absorbed dose extrapolation methods for mouse-to-human translation of radiolabelled macromolecules.
Extrapolation of human absorbed doses (ADs) from biodistribution experiments on laboratory animals is used to predict the efficacy and toxicity profiles of new radiopharmaceuticals. Comparative studies between available animal-to-human dosimetry extrapolation methods are missing. We compared five computational methods for mice-to-human AD extrapolations, using two different radiopharmaceuticals, namely [ <sup>111</sup> In]CHX-DTPA-scFv78-Fc and [ <sup>68</sup> Ga]NODAGA-RGDyK. Human organ-specific time-integrated activity coefficients (TIACs) were derived from biodistribution studies previously conducted in our centre. The five computational methods adopted are based on simple direct application of mice TIACs to human organs (M1), relative mass scaling (M2), metabolic time scaling (M3), combined mass and time scaling (M4), and organ-specific allometric scaling (M5), respectively. For [ <sup>68</sup> Ga]NODAGA-RGDyK, these methods for mice-to-human extrapolations were tested against the ADs obtained on patients, previously published by our group. Lastly, an average [ <sup>68</sup> Ga]NODAGA-RGDyK-specific allometric parameter α <sub>new</sub> was calculated from the organ-specific biological half-lives in mouse and humans and retrospectively applied to M3 and M4 to assess differences in human AD predictions with the α = 0.25 recommended by previous studies.
For both radiopharmaceuticals, the five extrapolation methods showed significantly different AD results (p < 0.0001). In general, organ ADs obtained with M3 were higher than those obtained with the other methods. For [ <sup>68</sup> Ga]NODAGA-RGDyK, no significant differences were found between ADs calculated with M3 and those obtained directly on human subjects (H) (p = 0.99; average M3/H AD ratio = 1.03). All other methods for dose extrapolations resulted in ADs significantly different from those calculated directly on humans (all p ≤ 0.0001). Organ-specific allometric parameters calculated using combined experimental [ <sup>68</sup> Ga]NODAGA-RGDyK mice and human biodistribution data varied significantly. ADs calculated with M3 and M4 after the application of α <sub>new</sub> = 0.17 were significantly different from those obtained by the application of α = 0.25 (both p < 0.001).
Available methods for mouse-to-human dosimetry extrapolations provided significantly different results in two different experimental models. For [ <sup>68</sup> Ga]NODAGA-RGDyK, the best approximation of human dosimetry was shown by M3, applying a metabolic scaling to the mouse organ TIACs. The accuracy of more refined extrapolation algorithms adopting model-specific metabolic scaling parameters should be further investigated
Internet-based ICRP resource for healthcare providers on the risks and benefits of medical imaging that uses ionising radiation
Specific absorbed fraction from Korean tomographic phantom for internally deposited photon source
Radiopeptide Therapy with Cholecystokinin(CCK)-B/Gastrin Receptor Ligands Labeled with Auger/Conversion Electron-versus alpha- or Conventional beta Emitters.
Abstract not availableJRC.E-Institute for Transuranium Elements (Karlsruhe
Whole-Body Biodistribution and Radiation Dosimetry of the New Cardiac Tracer 99mTc-N-DBODC
Our purpose was to evaluate the safety profile and biodistribution
behavior in healthy human volunteers of the new myocardial
perfusion tracer bis[(dimethoxypropylphosphanyl)ethyl]ethoxyethylamine
N,N9-bis(ethoxyethyl)dithiocarbamato nitrido technetium
(V) (99mTc-N-DBODC). Methods: Ten healthy male volunteers
were injected with 99mTc-N-DBODC under both stress and rest
conditions. Anterior and posterior planar g-camera images were
collected at 5, 30, 60, 240, and 1,440 min after injection, with organ
uptake quantified by region-of-interest analysis. Tracer kinetics
in body fluids were determined by collecting blood and urine
samples at different time points. Results: After injection, 99mTc-
N-DBODC showed significant accumulation in the myocardium
and prolonged retention. Under rest conditions, uptake in the
heart, lungs, and liver at 5 min after injection was 1.67% 6
0.13%, 1.16% 6 0.07%, and 10.85% 6 1.72%, respectively, of
administered activity. Under stress conditions, heart uptake was
significantly higher (2.07%6 0.22%). Radioactivity in the liver decreased
to 3.64%60.98%and 2.37%60.48%at 60 and 240 min,
respectively, after injection. This rapid liver clearance led to favorable
heart-to-liver ratios, reaching values of 0.7460.13 at rest and
1.2660.28 during exercise 60 min after tracer administration. Radiation
dose estimates were comparable to those obtained with
other myocardial perfusion cationic compounds. Conclusion:
The high uptake in the myocardium and the fast liver washout of
99mTc-N-DBODC will allow SPECT images of the left ventricle to
be acquired early and with excellent quality
Radiopeptide Therapy with Cholecystokinin-B/Gastrin Receptor Ligands: Dose-Limiting Toxicity and Therapeutic Efficacy of Auger / Conversion Electron (111-In, 140-Nd) vs alpha(213-Bi) or Conventional beta(90-Y, 153-Sm) Emitters.
Abstract not availableJRC.E-Institute for Transuranium Elements (Karlsruhe