In vivo quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept.

Objective . 225 Ac radiopharmaceuticals have tremendous potential for targeted alpha therapy, however, 225 Ac ( t 1/2 = 9.9 d) lacks direct gamma emissions for in vivo imaging. 226 Ac ( t 1/2 = 29.4 h) is a promising element-equivalent matched diagnostic radionuclide for preclinical evaluation of 225 Ac radiopharmaceuticals. 226 Ac has two gamma emissions (158 keV and 230 keV) suitable for SPECT imaging. This work is the first feasibility study for in vivo quantitative 226 Ac SPECT imaging and validation of activity estimation. Approach . 226 Ac was produced at TRIUMF (Vancouver, Canada) with its Isotope Separator and Accelerator (ISAC) facility. [ 226 Ac]Ac 3+ 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 [ 226 Ac]Ac-crown-TATE or 4 MBq of free [ 226 Ac]Ac 3+ 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 226 Ac 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 226 Ac activity distributions. Time-activity curves derived from SPECT images quantify the in vivo biodistribution of [ 226 Ac]Ac-crown-TATE and free [ 226 Ac]Ac 3+ 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.