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

Purpose Although( 221)Fr and Bi-213 have sufficient gamma emission probabilities, quantitative SPECT after [Ac-225]Ac-PSMA-I&T therapy remains challenging due to low therapeutic activities. Furthermore, Fr-221 and Bi-213 may underlie a different pharmacokinetics due to alpha recoil. We conducted a quantitative SPECT study and a urine analysis to investigate the pharmacokinetics of Fr-221 and Bi-213 and the impact on image-based lesion and kidney dosimetry. Methods Five patients (7.7 +/- 0.2 MBq [Ac-225]Ac-PSMA-I&T) underwent an abdominal SPECT/CT (1 h) at 24 and 48 h (Siemens Symbia T2, high-energy collimator, 440 keV/218 keV (width 20%), 78 keV (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 24 h) were fitted mono-exponentially. Urine samples collected along with each SPECT/CT were measured in a gamma counter until secular equilibrium was reached. Results Mean kidney and lesion effective half-lives were as follows: Bi-213, 27 +/- 6/38 +/- 10 h; Fr-221, 24 +/- 6/38 +/- 11 h; 78 keV, 23 +/- 7/39 +/- 13 h. The Bi-213-to-Fr-221 kidney SUV ratio increased by an average of 9% from 24 to 48 h. Urine analysis revealed an increasing Bi-213-to-Ac-225 ratio (24 h, 0.98 +/- 0.15; 48 h, 1.08 +/- 0.09). Mean kidney and lesion absorbed doses were 0.17 +/- 0.06 and 0.36 +/- 0.1 Sv(RBE=5)/MBq using Fr-221 and Bi-213 SPECT images, compared to 0.16 +/- 0.05/0.18 +/- 0.06 and 0.36 +/- 0.1/0.38 +/- 0.1 SvRBE=5/MBq considering either the( 221)Fr or 213Bi SPECT. Conclusion 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%.