{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T22:38:45Z","timestamp":1778452725272,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000015","name":"U.S. Department of Energy","doi-asserted-by":"publisher","award":["DE\u2010AC05\u201000OR22725"],"award-info":[{"award-number":["DE\u2010AC05\u201000OR22725"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A radiation dosimetry simulation was performed using a whole\u2010body 4D Extended Cardiac\u2010Torso (XCAT) phantom embedded in the GATE Monte Carlo platform. A 10\u2010mCi dose of <jats:sup>18<\/jats:sup>F\u2010FDG 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\u00a0mL rectangle in the hypodermal layer of skin. Absorbed dose contributions were calculated for the first two half\u2010lives, 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 <jats:sup>18<\/jats:sup>F and <jats:sup>68<\/jats:sup>Ga. 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\u2010nBio simulation to assess the extent of DNA damage, including double\u2010strand breaks (DSBs) and single\u2010strand breaks (SSBs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Organ\u2010level dosimetric estimations are presented for <jats:sup>18<\/jats:sup>F and <jats:sup>68<\/jats:sup>Ga radionuclides in various organs of interest. With 10% extravasation, the hypodermal layer of the skin received the highest absorbed dose of 1.32\u00a0\u00b1\u00a00.01\u00a0Gy for <jats:sup>18<\/jats:sup>F and 0.99\u00a0\u00b1\u00a00.01\u00a0Gy for <jats:sup>68<\/jats:sup>Ga. The epidermal and dermal layers received absorbed doses of 0.07\u00a0\u00b1\u00a00.01\u00a0Gy and 0.13\u00a0\u00b1\u00a00.01\u00a0Gy for <jats:sup>18<\/jats:sup>F, and 0.14\u00a0\u00b1\u00a00.01\u00a0Gy and 0.29\u00a0\u00b1\u00a00.01\u00a0Gy for <jats:sup>68<\/jats:sup>Ga, respectively. In the extravasated volume, <jats:sup>18<\/jats:sup>F caused an average absorbed dose per nucleus of 0.17\u00a0\u00b1\u00a00.01\u00a0Gy, estimated to result in 10.58\u00a0\u00b1\u00a00.50 DSBs and 268.11\u00a0\u00b1\u00a012.43 SSBs per nucleus. For <jats:sup>68<\/jats:sup>Ga, the absorbed dose per nucleus was 0.11\u00a0\u00b1\u00a00.01\u00a0Gy, leading to an estimated 6.49\u00a0\u00b1\u00a00.34 DSBs and 161.24\u00a0\u00b1\u00a08.12 SSBs per nucleus. Absorbed doses in other organs were on the order of micro\u2010gray (\u00b5Gy).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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\u2010level absorbed doses were found to be clinically insignificant across various simulated organs. The minimal DNA damage at the extravasation site suggests that long\u2010term harm, such as radiation\u2010induced carcinogenesis, is highly unlikely.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mp.17520","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T19:59:09Z","timestamp":1732132749000},"page":"801-813","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dosimetric and biological impact of activity extravasation of radiopharmaceuticals in PET imaging"],"prefix":"10.1002","volume":"52","author":[{"given":"Ashok","family":"Tiwari","sequence":"first","affiliation":[{"name":"Advanced Computing for Health Sciences Oak Ridge National Laboratory Oak Ridge Tennessee USA"},{"name":"Department of Radiation Oncology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Andriotty","sequence":"additional","affiliation":[{"name":"Department of Nuclear &amp; Radiological Engineering &amp; Medical Physics Georgia Institute of Technology Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greeshma","family":"Agasthya","sequence":"additional","affiliation":[{"name":"Department of Nuclear &amp; Radiological Engineering &amp; Medical Physics Georgia Institute of Technology Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.","family":"Sunderland","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Iowa Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dustin R.","family":"Osborne","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Tennessee Knoxville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anuj J.","family":"Kapadia","sequence":"additional","affiliation":[{"name":"Advanced Computing for Health Sciences Oak Ridge National Laboratory Oak Ridge Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Advancing Nuclear Medicine Through Innovation","author":"National Research Council (US) and Institute of Medicine (US) Committee on State of the Science of Nuclear Medicine","year":"2007"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2312021185"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12880-020-0408-3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnmt.119.228098"},{"issue":"840619","key":"e_1_2_9_6_1","article-title":"Dosimetric implications of the infiltrated injection","volume":"25","author":"Castronovo F","year":"1984","journal-title":"J Nucl Med;(United States)"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00253448"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-198503000-00017"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-017-3675-7"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.122.264994"},{"key":"e_1_2_9_11_1","unstructured":"Accessed Feb 10 https:\/\/www.regulations.gov\/comment\/NRC\u20102020\u20100141\u201004282023."},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/HP.0000000000001375"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.684157"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/HP.0000000000001653"},{"key":"e_1_2_9_15_1","unstructured":"Federal Register.Reporting nuclear medicine injection extravasations as medical events.Federal Register;2023. 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