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In vivo quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept
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DOI：10.1088/1361-6560/ad5c37.png)
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Abstract
En 中文
Objective. Ac-225 radiopharmaceuticals have tremendous potential for targeted alpha therapy, however, Ac-225 (t(1/2) = 9.9 d) lacks direct gamma emissions for in vivo imaging. Ac-226 (t(1/2) = 29.4 h) is a promising element-equivalent matched diagnostic radionuclide for preclinical evaluation of Ac-225 radiopharmaceuticals. Ac-226 has two gamma emissions (158 keV and 230 keV) suitable for SPECT imaging. This work is the first feasibility study for in vivo quantitative Ac-226 SPECT imaging and validation of activity estimation. Approach. Ac-226 was produced at TRIUMF (Vancouver, Canada) with its Isotope Separator and Accelerator (ISAC) facility. [Ac-226]Ac3+ was radiolabelled with the bioconjugate crown-TATE developed for therapeutic targeting of neuroendocrine tumours. Mice with AR42J tumour xenografts were injected with either 2 MBq of [Ac-226]Ac-crown-TATE or 4 MBq of free [Ac-226]Ac3+ activity and were scanned at 1, 2.5, 5, and 24 h post injection in a preclinical microSPECT/CT. Quantitative SPECT images were reconstructed from the 158 keV and 230 keV photopeaks with attenuation, background, and scatter corrections. Image-based Ac-226 activity measurements were assessed from volumes of interest within tumours and organs of interest. Imaging data was compared with ex vivo biodistribution measured via gamma counter. Main results. We present, to the best of our knowledge, the first ever in vivo quantitative SPECT images of Ac-226 activity distributions. Time-activity curves derived from SPECT images quantify the in vivo biodistribution of [Ac-226]Ac-crown-TATE and free [Ac-226]Ac3+ activity. Image-based activity measurements in the tumours and organs of interest corresponded well with ex vivo biodistribution measurements. Significance. Here in, we established the feasibility of in vivo(226)Ac quantitative SPECT imaging for accurate measurement of actinium biodistribution in a preclinical model. This imaging method could facilitate more efficient development of novel actinium labelled compounds by providing accurate quantitative in vivo pharmacokinetic information essential for estimating toxicities, dosimetry, and therapeutic potency.
Keywords:
actinium-226
preclinical imaging
quantitative SPECT
theranostics
actinium-225
Journal
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