{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:07:44Z","timestamp":1784758064490,"version":"3.55.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p><jats:sup>223<\/jats:sup>Ra is currently used for treatment of metastatic castration resistant prostate cancer patients (mCRPC) bone metastases with fixed standard activity. Individualized treatments, based on adsorbed dose (AD) in target and non-target tissue, are absolutely needed to optimize efficacy while reducing toxicity of \u03b1-emitter targeted therapy. This is a pilot first in human clinical trial aimed to correlate dosimetry, clinical response and biological side effects to personalize <jats:sup>223<\/jats:sup>Ra treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Out of 20 mCRPC patients who underwent standard <jats:sup>223<\/jats:sup>Ra treatment and dosimetry, in a subset of 5 patients the AD to target and non-target tissues was correlated with clinical effects and radiation-induced chromosome damages. Before each <jats:sup>223<\/jats:sup>Ra administrations, haematological parameters, PSA and ALP values were evaluated. Additional blood samples were obtained baseline (T0), at 7\u2009days (T7), 30\u2009days (T30) and 180\u2009days (T180) to evaluate chromosome damage. After administration WB planar <jats:sup>223<\/jats:sup>Ra images were obtained at 2\u20134 and 18\u201324\u2009h. Treatment response and toxicity were monitored with clinical evaluation, bone scan, 18F-choline-PET\/CT, PSA value and ALP while haematological parameters were evaluated weekly after <jats:sup>223<\/jats:sup>Ra injection and 2\u00a0months after last cycle.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>1. a correlation between AD to target and clinical response was evidenced with threshold of 20\u2009Gy as a cut-off to obtain tumor control; 2. the AD to red marrow was lower than 2\u2009Gy in all the patients with no apparently correlation between dosimetry and clinical toxicity. 3. a high dose dependent increase of the number of dicentrics and micronuclei during the course of <jats:sup>223<\/jats:sup>Ra therapy was observed and a linear correlation has been found between blood AD (BAD) and number of dicentrics.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study provides some interesting preliminary evidence to be further investigated: dosimetry may be useful to identify a more appropriate <jats:sup>223<\/jats:sup>Ra administered activity predicting AD to target tissue; a dose dependent complex chromosome damage occurs during <jats:sup>223<\/jats:sup>Ra administration and this injury is more evident in heavily pre-treated patients; dosimetry could be used for radioprotection purpose.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>The pilot study has been approved from the Ethics Committee of Regina Elena National Cancer Institute (N:RS1083\/18\u20132111).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13046-021-02056-9","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T09:03:04Z","timestamp":1630918984000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The role of dosimetry and biological effects in metastatic castration\u2013resistant prostate cancer (mCRPC) patients treated with 223Ra: first in human study"],"prefix":"10.1186","volume":"40","author":[{"given":"Rosa","family":"Sciuto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Rea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ungania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Testa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Dini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonella","family":"Tabocchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarice","family":"Patrono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Soriani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Palma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Marconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4293-2298","authenticated-orcid":false,"given":"Lidia","family":"Strigari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"2056_CR1","doi-asserted-by":"publisher","unstructured":"Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Foss\u00e5 SD, et al. 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