TY - JOUR
T1 - Single-Time-Point Renal Dosimetry Using Nonlinear Mixed-Effects Modeling and Population-Based Model Selection in [177Lu]Lu-PSMA-617 Therapy
AU - Hardiansyah, Deni
AU - Yousefzadeh-Nowshahr, Elham
AU - Kind, Felix
AU - Beer, Ambros J.
AU - Ruf, Juri
AU - Glatting,
AU - Mix, Michael
N1 - Publisher Copyright:
© 2024 by the Society of Nuclear Medicine andMolecular Imaging.
PY - 2024
Y1 - 2024
N2 - The aim of this study was to investigate the accuracy of single-timepoint (STP) renal dosimetry imaging using SPECT/CT data, a nonlinear mixed-effects (NLME)model, and a population-basedmodel selection (PBMS) in a large population for 177Lu-labeled prostate-specific membrane antigen therapy. Methods: Biokinetic data (mean 6 SD) of [177Lu]Lu-PSMA-617 in kidneys at time points 1 (1.860.8 h), 2 (18.760.9 h), 3 (42.661.0 h), 4 (66.360.9 h), and 5 (160.3624.2 h) after injection were obtained from 63 patients with metastatic castration-resistant prostate cancer using SPECT/CT. Thirteen functions were derived from various parameterizations of 1- to 5-exponential functions. The function's parameters were fitted in the NLME framework to the all-time-point (ATP) data. The PBMS NLME method was performed using the goodness-of-fit test and Akaike weight to select the best function fitting the data. The best function from ATP fitting was used to calculate the reference time-integrated activity and absorbed doses. In STP dosimetry, the parameters of a particular patient with STP data were fitted simultaneously to the STP data at different time points of that patient with ATP data of all other patients. The parameters from STP fitting were used to calculate the STP time-integrated activity and absorbed doses. Relative deviations (RDs) and root-mean-square errors (RMSEs) were used to analyze the accuracy of the calculated STP absorbed dose compared with the reference absorbed dose obtained from the best-fit ATP function. The performance of STP dosimetry using PBMS NLME modeling was compared with the Hänscheid and Madsen methods. Results: The function A1 e2(l1 1λphys)t1A2 e2(l2 1λphys)t2A3 e2(l3 1λphys)t2(A11A22A3) e2(λbc +λphys)t was selected as the best-fit ATP function, with an Akaike weight of 100%. For STP dosimetry, the STP measurement by SPECT/CT at time point 3 (42.661.0h) showed a relatively low mean RD of 24.4% 6 9.4% and median RD of 20.7%. Time point 3 had the lowest RMSE value compared with those at the other 4 time points. The RMSEs of the absorbed dose RDs for time points 1-5 were 23%, 16%, 10%, 20%, and 53%, respectively. The STP dosimetry using the PBMS NLME method outperformed the Hänscheid and Madsen methods for all investigated time points. Conclusion: Our results show that a singlemeasurement of SPECT/CT at 2 d after injection might be used to calculate accurate kidney-absorbed doses using the NLMEmethod and PBMS.
AB - The aim of this study was to investigate the accuracy of single-timepoint (STP) renal dosimetry imaging using SPECT/CT data, a nonlinear mixed-effects (NLME)model, and a population-basedmodel selection (PBMS) in a large population for 177Lu-labeled prostate-specific membrane antigen therapy. Methods: Biokinetic data (mean 6 SD) of [177Lu]Lu-PSMA-617 in kidneys at time points 1 (1.860.8 h), 2 (18.760.9 h), 3 (42.661.0 h), 4 (66.360.9 h), and 5 (160.3624.2 h) after injection were obtained from 63 patients with metastatic castration-resistant prostate cancer using SPECT/CT. Thirteen functions were derived from various parameterizations of 1- to 5-exponential functions. The function's parameters were fitted in the NLME framework to the all-time-point (ATP) data. The PBMS NLME method was performed using the goodness-of-fit test and Akaike weight to select the best function fitting the data. The best function from ATP fitting was used to calculate the reference time-integrated activity and absorbed doses. In STP dosimetry, the parameters of a particular patient with STP data were fitted simultaneously to the STP data at different time points of that patient with ATP data of all other patients. The parameters from STP fitting were used to calculate the STP time-integrated activity and absorbed doses. Relative deviations (RDs) and root-mean-square errors (RMSEs) were used to analyze the accuracy of the calculated STP absorbed dose compared with the reference absorbed dose obtained from the best-fit ATP function. The performance of STP dosimetry using PBMS NLME modeling was compared with the Hänscheid and Madsen methods. Results: The function A1 e2(l1 1λphys)t1A2 e2(l2 1λphys)t2A3 e2(l3 1λphys)t2(A11A22A3) e2(λbc +λphys)t was selected as the best-fit ATP function, with an Akaike weight of 100%. For STP dosimetry, the STP measurement by SPECT/CT at time point 3 (42.661.0h) showed a relatively low mean RD of 24.4% 6 9.4% and median RD of 20.7%. Time point 3 had the lowest RMSE value compared with those at the other 4 time points. The RMSEs of the absorbed dose RDs for time points 1-5 were 23%, 16%, 10%, 20%, and 53%, respectively. The STP dosimetry using the PBMS NLME method outperformed the Hänscheid and Madsen methods for all investigated time points. Conclusion: Our results show that a singlemeasurement of SPECT/CT at 2 d after injection might be used to calculate accurate kidney-absorbed doses using the NLMEmethod and PBMS.
KW - Akaike weight
KW - model selection
KW - NLME modeling
KW - PSMA
KW - STP dosimetry
UR - http://www.scopus.com/inward/record.url?scp=85189202113&partnerID=8YFLogxK
U2 - 10.2967/jnumed.123.266268
DO - 10.2967/jnumed.123.266268
M3 - Article
C2 - 38423787
AN - SCOPUS:85189202113
SN - 0161-5505
VL - 65
SP - 566
EP - 572
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 4
ER -