Single-Time-Point Renal Dosimetry Using Nonlinear Mixed-Effects Modeling and Population-Based Model Selection in [177Lu]Lu-PSMA-617 Therapy. 2024

Deni Hardiansyah, and Elham Yousefzadeh-Nowshahr, and Felix Kind, and Ambros J Beer, and Juri Ruf, and Gerhard Glatting, and Michael Mix
Medical Physics and Biophysics, Physics Department, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok, Indonesia; denihardiansyah@ui.ac.id.

The aim of this study was to investigate the accuracy of single-time-point (STP) renal dosimetry imaging using SPECT/CT data, a nonlinear mixed-effects (NLME) model, and a population-based model selection (PBMS) in a large population for 177Lu-labeled prostate-specific membrane antigen therapy. Methods: Biokinetic data (mean ± SD) of [177Lu]Lu-PSMA-617 in kidneys at time points 1 (1.8 ± 0.8 h), 2 (18.7 ± 0.9 h), 3 (42.6 ± 1.0 h), 4 (66.3 ± 0.9 h), and 5 (160.3 ± 24.2 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 [Formula: see text] 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 (42.6 ± 1.0 h) showed a relatively low mean RD of -4.4% ± 9.4% and median RD of -0.7%. 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 single measurement of SPECT/CT at 2 d after injection might be used to calculate accurate kidney-absorbed doses using the NLME method and PBMS.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008187 Lutetium An element of the rare earth family of metals. It has the atomic symbol Lu, atomic number 71, and atomic weight 175.
D008297 Male Males
D004151 Dipeptides Peptides composed of two amino acid units. Dipeptide
D006573 Heterocyclic Compounds, 1-Ring Organic compounds that contain a ring structure made up of carbon and one or more additional elements such as nitrogen and oxygen. Heterocyclic Cpds, 1-Ring,1-Ring Heterocyclic Compounds,1-Ring Heterocyclic Cpds,Heterocyclic Compounds, 1 Ring,Heterocyclic Cpds, 1 Ring
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D017430 Prostate-Specific Antigen A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Kallikrein hK3,gamma-Seminoprotein,hK3 Kallikrein,Prostate Specific Antigen,Semenogelase,Seminin,Kallikrein, hK3,gamma Seminoprotein
D019275 Radiopharmaceuticals Compounds that are used in medicine as sources of radiation for radiotherapy and for diagnostic purposes. They have numerous uses in research and industry. (Martindale, The Extra Pharmacopoeia, 30th ed, p1161) Radiopharmaceutical
D064129 Prostatic Neoplasms, Castration-Resistant Tumors or cancer of the PROSTATE which can grow in the presence of low or residual amount of androgen hormones such as TESTOSTERONE. Androgen-Independent Prostatic Cancer,Androgen-Independent Prostatic Neoplasms,Androgen-Insensitive Prostatic Cancer,Androgen-Insensitive Prostatic Neoplasms,Androgen-Resistant Prostatic Cancer,Androgen-Resistant Prostatic Neoplasms,Castration-Resistant Prostatic Cancer,Castration-Resistant Prostatic Neoplasms,Hormone Refractory Prostatic Cancer,Hormone Refractory Prostatic Neoplasms,Prostatic Cancer, Androgen-Independent,Prostatic Cancer, Androgen-Insensitive,Prostatic Cancer, Androgen-Resistant,Prostatic Cancer, Castration-Resistant,Prostatic Cancer, Hormone Refractory,Prostatic Neoplasms, Androgen-Independent,Prostatic Neoplasms, Androgen-Insensitive,Prostatic Neoplasms, Androgen-Resistant,Prostatic Neoplasms, Hormone Refractory,Androgen Independent Prostatic Cancer,Androgen Independent Prostatic Neoplasms,Androgen Insensitive Prostatic Cancer,Androgen Insensitive Prostatic Neoplasms,Androgen Resistant Prostatic Cancer,Androgen Resistant Prostatic Neoplasms,Androgen-Independent Prostatic Cancers,Androgen-Independent Prostatic Neoplasm,Androgen-Insensitive Prostatic Cancers,Androgen-Insensitive Prostatic Neoplasm,Androgen-Resistant Prostatic Cancers,Androgen-Resistant Prostatic Neoplasm,Cancer, Androgen-Independent Prostatic,Cancer, Androgen-Insensitive Prostatic,Cancer, Androgen-Resistant Prostatic,Cancer, Castration-Resistant Prostatic,Cancers, Androgen-Independent Prostatic,Cancers, Androgen-Insensitive Prostatic,Cancers, Androgen-Resistant Prostatic,Cancers, Castration-Resistant Prostatic,Castration Resistant Prostatic Cancer,Castration Resistant Prostatic Neoplasms,Castration-Resistant Prostatic Cancers,Castration-Resistant Prostatic Neoplasm,Neoplasm, Androgen-Independent Prostatic,Neoplasm, Androgen-Insensitive Prostatic,Neoplasm, Androgen-Resistant Prostatic,Neoplasm, Castration-Resistant Prostatic,Neoplasms, Androgen-Independent Prostatic,Neoplasms, Androgen-Insensitive Prostatic,Neoplasms, Androgen-Resistant Prostatic,Neoplasms, Castration-Resistant Prostatic,Prostatic Cancer, Androgen Independent,Prostatic Cancer, Androgen Insensitive,Prostatic Cancer, Androgen Resistant,Prostatic Cancer, Castration Resistant,Prostatic Cancers, Androgen-Independent,Prostatic Cancers, Androgen-Insensitive,Prostatic Cancers, Androgen-Resistant,Prostatic Cancers, Castration-Resistant,Prostatic Neoplasm, Androgen-Independent,Prostatic Neoplasm, Androgen-Insensitive,Prostatic Neoplasm, Androgen-Resistant,Prostatic Neoplasm, Castration-Resistant,Prostatic Neoplasms, Androgen Independent,Prostatic Neoplasms, Androgen Insensitive,Prostatic Neoplasms, Androgen Resistant,Prostatic Neoplasms, Castration Resistant

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