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

• Published in: European journal of nuclear medicine and molecular imaging 2024-07, Vol.51 (8), p.2504-2514
• Main Authors: Liubchenko, Grigory, Böning, Guido, Zacherl, Mathias, Rumiantcev, Mikhail, Unterrainer, Lena M., Gildehaus, Franz Josef, Brendel, Matthias, Resch, Sandra, Bartenstein, Peter, Ziegler, Sibylle I., Delker, Astrid
• Format: Article
• Language: English
• Subjects: Actinium - chemistry; Actinium - pharmacokinetics; Aged; Bismuth isotopes; Cardiology; Computed tomography; Dosimeters; Dosimetry; Gamma emission; Glutamate Carboxypeptidase II - metabolism; Humans; Imaging; Kidney - diagnostic imaging; Kidney - metabolism; Kidneys; Lesions; Male; Medical imaging; Medicine; Medicine & Public Health; Middle Aged; Nuclear Medicine; Oncology; Original; Original Article; Orthopedics; Pharmacokinetics; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - radiotherapy; Radioisotopes - pharmacokinetics; Radioisotopes - therapeutic use; Radiology; Radiometry; Radiopharmaceuticals - pharmacokinetics; Single photon emission computed tomography; Single Photon Emission Computed Tomography Computed Tomography; Urine
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-024-06681-2

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 Sv RBE = 5 /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 Sv RBE = 5 /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%.