Abstract
The aim was to investigate the induction and repair of radiation-induced DNA double-strand breaks (DSBs) as a function of the absorbed dose to the blood of patients undergoing PET/CT examinations with [68Ga]Ga-PSMA. Blood samples were collected from 15 patients before and at four time points after [68Ga]Ga-PSMA administration, both before and after the PET/CT scan. Absorbed doses to the blood were calculated. In addition, blood samples with/without contrast agent from five volunteers were irradiated ex vivo by CT while measuring the absorbed dose. Leukocytes were isolated, fixed, and stained for co-localizing γ-H2AX+53BP1 DSB foci that were enumerated manually. In vivo, a significant increase in γ-H2AX+53BP1 foci compared to baseline was observed at all time points after administration, although the absorbed dose to the blood by 68Ga was below 4 mGy. Ex vivo, the increase in radiation-induced foci depended on the absorbed dose and the presence of contrast agent, which could have caused a dose enhancement. The CT-dose contribution for the patients was estimated at about 12 mGy using the ex vivo calibration. The additional number of DSB foci induced by CT, however, was comparable to the one induced by 68Ga. The significantly increased foci numbers after [68Ga]Ga-PSMA administration may suggest a possible low-dose hypersensitivity.
Highlights
PET/computed tomography tomography (CT) with 68 Ga-labelled prostate-specific membrane antigen (PSMA) is a non-invasive diagnostic technique to image prostate cancer patients with increased PSMA expression [1]
Among others, [68 Ga]Ga-PSMA I&T is of interest, as it can be labelled with 177 Lu for therapeutic purposes [2,3]
Focus assay with the absorbed doses to the blood after administration of [68 Ga]Ga-PSMA I&T, we were able to show that even at very low absorbed doses to the blood of less than 3 mGy, the number of double strand breaks (DSBs) in the blood is significantly increased compared to baseline
Summary
PET/CT with 68 Ga-labelled prostate-specific membrane antigen (PSMA) is a non-invasive diagnostic technique to image prostate cancer patients with increased PSMA expression [1]. Foci in the first few hours after administration of the radiopharmaceutical, followed by a phase of equilibrium between repair and induction of DSBs, and subsequently by predominant repair leading, in most patients, to a complete decline to baseline foci levels [7,8,9] Our group applied this DSB damage assay successfully in a number of ex vivo and in vivo studies with different therapeutic radionuclides such as 131 I, 177 Lu and the radium isotopes 223 Ra and 224 Ra [7,8,9,10,11,12,13]
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