Dosimetric and biological impact of activity extravasation of radiopharmaceuticals in PET imaging

Ashok Tiwari, Matthew Andriotty, Greeshma Agasthya, John J. Sunderland, Dustin R. Osborne, Anuj J. Kapadia

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The increasing use of nuclear medicine and PET imaging has intensified scrutiny of radiotracer extravasation. To our knowledge, this topic is understudied but holds great potential for enhancing our understanding of extravasation in clinical PET imaging. Purpose: This work aims to (1) quantify the absorbed doses from radiotracer extravasation in PET imaging, both locally at the site of extravasation and with the extravasation location as a source of exposure to bodily organs and (2) assess the biological ramifications within the injection site at the cellular level. Methods: A radiation dosimetry simulation was performed using a whole-body 4D Extended Cardiac-Torso (XCAT) phantom embedded in the GATE Monte Carlo platform. A 10-mCi dose of 18F-FDG was chosen to simulate a typical clinical PET scan scenario, with 10% of the activity extravasated in the antecubital fossa of the right arm of the phantom. The extravasation volume was modeled as a 5.5 mL rectangle in the hypodermal layer of skin. Absorbed dose contributions were calculated for the first two half-lives, assuming biological clearance thereafter. Dose calculations were performed as absorbed doses at the organ and skin levels. Energy deposition was simulated both at the local extravasation site and in multiple organs of interest and converted to absorbed doses based on their respective masses. Each simulation was repeated ten times to estimate Monte Carlo uncertainties. Biological impacts on cells within the extravasated volume were evaluated by randomizing cells and exposing them to a uniform radiation source of 18F and 68Ga. Particle types, their energies, and direction cosines were recorded in phase space files using a separate Geant4 simulation to characterize their entry into the nucleus of the cellular volume. Subsequently, the phase space files were imported into the TOPAS-nBio simulation to assess the extent of DNA damage, including double-strand breaks (DSBs) and single-strand breaks (SSBs). Results: Organ-level dosimetric estimations are presented for 18F and 68Ga radionuclides in various organs of interest. With 10% extravasation, the hypodermal layer of the skin received the highest absorbed dose of 1.32 ± 0.01 Gy for 18F and 0.99 ± 0.01 Gy for 68Ga. The epidermal and dermal layers received absorbed doses of 0.07 ± 0.01 Gy and 0.13 ± 0.01 Gy for 18F, and 0.14 ± 0.01 Gy and 0.29 ± 0.01 Gy for 68Ga, respectively. In the extravasated volume, 18F caused an average absorbed dose per nucleus of 0.17 ± 0.01 Gy, estimated to result in 10.58 ± 0.50 DSBs and 268.11 ± 12.43 SSBs per nucleus. For 68Ga, the absorbed dose per nucleus was 0.11 ± 0.01 Gy, leading to an estimated 6.49 ± 0.34 DSBs and 161.24 ± 8.12 SSBs per nucleus. Absorbed doses in other organs were on the order of micro-gray (µGy). Conclusion: The likelihood of epidermal erythema resulting from extravasation during PET imaging is low, as the simulated absorbed doses to the epidermis remain below the thresholds that trigger such effects. Moreover, the organ-level absorbed doses were found to be clinically insignificant across various simulated organs. The minimal DNA damage at the extravasation site suggests that long-term harm, such as radiation-induced carcinogenesis, is highly unlikely.

Original languageEnglish
JournalMedical Physics
DOIs
StateAccepted/In press - 2024

Funding

This work was supported by the Department of Energy (DOE)\u2019s Office of Biological and Environmental Research (BER), Biological Systems Science Division (BSSD), and Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT\u2010Battelle, LLC, for the U.S. Department of Energy. This research used resources from the Compute and Data Environment for Science (CADES) at the Oak Ridge National Laboratory. This manuscript has been authored by UT\u2010Battelle, LLC under Contract No. DE\u2010AC05\u201000OR22725 with the U.S. Department of Energy.

FundersFunder number
Laboratory Directed Research and Development Program
Biological and Environmental Research
Oak Ridge National Laboratory
U.S. Department of Energy
Biological Systems Science Division

    Keywords

    • absorbed dose
    • DNA strand breaks
    • extravasation dosimetry
    • Monte Carlo
    • XCAT phantom

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