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

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 ± 0.2 MBq [²²⁵Ac]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.

Mean kidney and lesion effective half-lives were as follows: ²¹³Bi, 27 ± 6/38 ± 10 h; ²²¹Fr, 24 ± 6/38 ± 11 h; 78 keV, 23 ± 7/39 ± 13 h. The ²¹³Bi-to-²²¹Fr kidney SUV ratio increased by an average of 9% from 24 to 48 h. Urine analysis revealed an increasing ²¹³Bi-to-²²⁵Ac 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 ${\text{Sv}}_{\text{RBE}=5}$ /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 ${\text{Sv}}_{\text{RBE}=5}$ /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%.