Image-based dosimetry for [225Ac]Ac-PSMA-I&T therapy and the effect of daughter-specific pharmacokinetics.

Abstract

Although 221Fr and 213Bi have sufficient gamma emission probabilities, quantitative SPECT after [225Ac]Ac-PSMA-I&T therapy remains challenging due to low therapeutic activities. Furthermore, 221Fr and 213Bi may underlie a different pharmacokinetics due to alpha recoil. We conducted a quantitative SPECT study and a urine analysis to investigate the pharmacokinetics of 221Fr and 213Bi and the impact on image-based lesion and kidney dosimetry. Five patients (7.7 ± 0.2MBq [225Ac]Ac-PSMA-I&T) underwent an abdominal SPECT/CT (1h) at 24 and 48h (Siemens Symbia T2, high-energy collimator, 440keV/218keV (width 20%), 78keV (width 50%)). Quantitative SPECT was reconstructed using MAP-EM with attenuation and transmission-dependent scatter corrections and resolution modelling. Time-activity curves for kidneys (CT-based) and lesions (80% isocontour 24h) were fitted mono-exponentially. Urine samples collected along with each SPECT/CT were measured in a gamma counter until secular equilibrium was reached. Mean kidney and lesion effective half-lives were as follows: 213Bi, 27 ± 6/38 ± 10h; 221Fr, 24 ± 6/38 ± 11h; 78keV, 23 ± 7/39 ± 13h. The 213Bi-to-221Fr kidney SUV ratio increased by an average of 9% from 24 to 48h. Urine analysis revealed an increasing 213Bi-to-225Ac ratio (24h, 0.98 ± 0.15; 48h, 1.08 ± 0.09). Mean kidney and lesion absorbed doses were 0.17 ± 0.06 and 0.36 ± 0.1 /MBq using 221Fr and 213Bi SPECT images, compared to 0.16 ± 0.05/0.18 ± 0.06 and 0.36 ± 0.1/0.38 ± 0.1 /MBq considering either the 221Fr or 213Bi SPECT. SPECT/CT imaging and urine analysis showed minor differences of up to 10% in the daughter-specific pharmacokinetics. These variances had a minimal impact on the lesion and kidney dosimetry which remained within 8%.