Image-based dosimetry for [225Ac]Ac-PSMA-I&T therapy and the effect of daughter-specific pharmacokinetics
Grigory Liubchenko, Guido Böning, Mathias J. Zacherl, Mikhail Rumiantcev, Lena M. Unterrainer, Franz Josef Gildehaus, Matthias Brendel, Sandra Resch, Peter Bartenstein, Sibylle Ziegler, Astrid Delker
Abstract
Abstract Purpose Although 221 Fr and 213 Bi have sufficient gamma emission probabilities, quantitative SPECT after [ 225 Ac]Ac-PSMA-I&T therapy remains challenging due to low therapeutic activities. Furthermore, 221 Fr and 213 Bi may underlie a different pharmacokinetics due to alpha recoil. We conducted a quantitative SPECT study and a urine analysis to investigate the pharmacokinetics of 221 Fr and 213 Bi and the impact on image-based lesion and kidney dosimetry. Methods Five patients (7.7 ± 0.2 MBq [ 225 Ac]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: 213 Bi, 27 ± 6/38 ± 10 h; 221 Fr, 24 ± 6/38 ± 11 h; 78 keV, 23 ± 7/39 ± 13 h. The 213 Bi-to- 221 Fr kidney SUV ratio increased by an average of 9% from 24 to 48 h. Urine analysis revealed an increasing 213 Bi-to- 225 Ac 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 $${{\text{Sv}}}_{{\text{RBE}}=5}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mtext>Sv</mml:mtext> <mml:mrow> <mml:mtext>RBE</mml:mtext> <mml:mo>=</mml:mo> <mml:mn>5</mml:mn> </mml:mrow> </mml:msub> </mml:math> /MBq using 221 Fr and 213 Bi SPECT images, compared to 0.16 ± 0.05/0.18 ± 0.06 and 0.36 ± 0.1/0.38 ± 0.1 $${{\text{Sv}}}_{{\text{RBE}}=5}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mtext>Sv</mml:mtext> <mml:mrow> <mml:mtext>RBE</mml:mtext> <mml:mo>=</mml:mo> <mml:mn>5</mml:mn> </mml:mrow> </mml:msub> </mml:math> /MBq considering either the 221 Fr or 213 Bi 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%.