In vivoquantitative SPECT imaging of actinium-226: feasibility and proof-of-concept

Objective.²²⁵Ac radiopharmaceuticals have tremendous potential for targeted alpha therapy, however,²²⁵Ac (t_1/2= 9.9 d) lacks direct gamma emissions forin vivoimaging.²²⁶Ac (t_1/2= 29.4 h) is a promising element-equivalent matched diagnostic radionuclide for preclinical evaluation of²²⁵Ac radiopharmaceuticals.²²⁶Ac has two gamma emissions (158 keV and 230 keV) suitable for SPECT imaging. This work is the first feasibility study forin vivoquantitative²²⁶Ac SPECT imaging and validation of activity estimation.Approach.²²⁶Ac was produced at TRIUMF (Vancouver, Canada) with its Isotope Separator and Accelerator (ISAC) facility. [²²⁶Ac]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 [²²⁶Ac]Ac-crown-TATE or 4 MBq of free [²²⁶Ac]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-based²²⁶Ac activity measurements were assessed from volumes of interest within tumours and organs of interest. Imaging data was compared withex vivobiodistribution measured via gamma counter.Main results. We present, to the best of our knowledge, the first everin vivoquantitative SPECT images of²²⁶Ac activity distributions. Time-activity curves derived from SPECT images quantify thein vivobiodistribution of [²²⁶Ac]Ac-crown-TATE and free [²²⁶Ac]Ac³⁺activity. Image-based activity measurements in the tumours and organs of interest corresponded well withex vivobiodistribution measurements.Significance. Here in, we established the feasibility ofin vivo²²⁶Ac 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 quantitativein vivopharmacokinetic information essential for estimating toxicities, dosimetry, and therapeutic potency.