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Background   223 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 α-emitter targeted therapy. This is a pilot first in human clinical trial aimed to correlate dosimetry, clinical response and biological side effects to personalize  223 Ra treatment.    Methods  Out of 20 mCRPC patients who underwent standard  223 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  223 Ra administrations, haematological parameters, PSA and ALP values were evaluated. Additional blood samples were obtained baseline (T0), at 7 days (T7), 30 days (T30) and 180 days (T180) to evaluate chromosome damage. After administration WB planar  223 Ra images were obtained at 2–4 and 18–24 h. 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  223 Ra injection and 2 months after last cycle.    Results  1. a correlation between AD to target and clinical response was evidenced with threshold of 20 Gy as a cut-off to obtain tumor control; 2. the AD to red marrow was lower than 2 Gy 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  223 Ra therapy was observed and a linear correlation has been found between blood AD (BAD) and number of dicentrics.    Conclusions  This study provides some interesting preliminary evidence to be further investigated: dosimetry may be useful to identify a more appropriate  223 Ra administered activity predicting AD to target tissue; a dose dependent complex chromosome damage occurs during  223 Ra administration and this injury is more evident in heavily pre-treated patients; dosimetry could be used for radioprotection purpose.    Trial registration  The pilot study has been approved from the Ethics Committee of Regina Elena National Cancer Institute (N:RS1083/18–2111).    Supplementary Information  The online version contains supplementary material available at 10.1186/s13046-021-02056-9.

journal of experimental and clinical cancer research

The role of dosimetry and biological effects in metastatic castration–resistant prostate cancer (mCRPC) patients treated with 223Ra: first in human study