TY - JOUR
T1 - In Vivo Biokinetics of 177Lu-OPS201 in Mice and Pigs as a Model for Predicting Human Dosimetry
AU - Beykan, Seval
AU - Fani, Melpomeni
AU - Jensen, Svend Borup
AU - Nicolas, Guillaume
AU - Wild, Damian
AU - Kaufmann, Jens
AU - Lassmann, Michael
PY - 2019
Y1 - 2019
N2 - Introduction.
177 Lu-OPS201 is a high-affinity somatostatin receptor subtype 2 antagonist for PRRT in patients with neuroendocrine tumors. The aim is to find the optimal scaling for dosimetry and to compare the biokinetics of
177 Lu-OPS201 in animals and humans. Methods. Data on biokinetics of
177 Lu-OPS201 were analyzed in athymic nude Foxn1
nu mice (28 F, weight: 26 ± 1 g), Danish Landrace pigs (3 F-1 M, weight: 28 ± 2 kg), and patients (3 F-1 M, weight: 61 ± 17 kg) with administered activities of 0.19–0.27 MBq (mice), 97–113 MBq (pigs), and 850–1086 MBq (patients). After euthanizing mice (up to 168 h), the organ-specific activity contents (including blood) were measured. Multiple planar and SPECT/CT scans were performed until 250 h (pigs) and 72 h (patients) to quantify the uptake in the kidneys and liver. Blood samples were taken up to 23 h (patients) and 300 h (pigs). In pigs and patients, kidney protection was applied. Time-dependent uptake data sets were created for each species and organ/tissue. Biexponential fits were applied to compare the biokinetics in the kidneys, liver, and blood of each species. The time-integrated activity coefficients (TIACs) were calculated by using NUKFIT. To determine the optimal scaling, several methods (relative mass scaling, time scaling, combined mass and time scaling, and allometric scaling) were compared. Results. A fast blood clearance of the compound was observed in the first phase (<56 h) for all species. In comparison with patients, pigs showed higher liver retention. Based on the direct comparison of the TIACs, an underestimation in mice (liver and kidneys) and an overestimation in pigs’ kidneys compared to the patient data (kidney TIAC: mice 1.4 h, pigs 7.7 h, and patients 5.8 h; liver TIAC: mice 0.7 h, pigs 4.1 h, and patients 5.3 h) were observed. Most similar TIACs were obtained by applying time scaling (mice) and combined scaling (pigs) (kidney TIAC: mice 3.9 h, pigs 4.8 h, and patients 5.8 h; liver TIAC: mice 0.9 h, pigs 4.7 h, and patients 5.3 h). Conclusion. If the organ mass ratios between the species are high, the combined mass and time scaling method is optimal to minimize the interspecies differences. The analysis of the fit functions and the TIACs shows that pigs are better mimicking human biokinetics.
AB - Introduction.
177 Lu-OPS201 is a high-affinity somatostatin receptor subtype 2 antagonist for PRRT in patients with neuroendocrine tumors. The aim is to find the optimal scaling for dosimetry and to compare the biokinetics of
177 Lu-OPS201 in animals and humans. Methods. Data on biokinetics of
177 Lu-OPS201 were analyzed in athymic nude Foxn1
nu mice (28 F, weight: 26 ± 1 g), Danish Landrace pigs (3 F-1 M, weight: 28 ± 2 kg), and patients (3 F-1 M, weight: 61 ± 17 kg) with administered activities of 0.19–0.27 MBq (mice), 97–113 MBq (pigs), and 850–1086 MBq (patients). After euthanizing mice (up to 168 h), the organ-specific activity contents (including blood) were measured. Multiple planar and SPECT/CT scans were performed until 250 h (pigs) and 72 h (patients) to quantify the uptake in the kidneys and liver. Blood samples were taken up to 23 h (patients) and 300 h (pigs). In pigs and patients, kidney protection was applied. Time-dependent uptake data sets were created for each species and organ/tissue. Biexponential fits were applied to compare the biokinetics in the kidneys, liver, and blood of each species. The time-integrated activity coefficients (TIACs) were calculated by using NUKFIT. To determine the optimal scaling, several methods (relative mass scaling, time scaling, combined mass and time scaling, and allometric scaling) were compared. Results. A fast blood clearance of the compound was observed in the first phase (<56 h) for all species. In comparison with patients, pigs showed higher liver retention. Based on the direct comparison of the TIACs, an underestimation in mice (liver and kidneys) and an overestimation in pigs’ kidneys compared to the patient data (kidney TIAC: mice 1.4 h, pigs 7.7 h, and patients 5.8 h; liver TIAC: mice 0.7 h, pigs 4.1 h, and patients 5.3 h) were observed. Most similar TIACs were obtained by applying time scaling (mice) and combined scaling (pigs) (kidney TIAC: mice 3.9 h, pigs 4.8 h, and patients 5.8 h; liver TIAC: mice 0.9 h, pigs 4.7 h, and patients 5.3 h). Conclusion. If the organ mass ratios between the species are high, the combined mass and time scaling method is optimal to minimize the interspecies differences. The analysis of the fit functions and the TIACs shows that pigs are better mimicking human biokinetics.
UR - http://www.scopus.com/inward/record.url?scp=85061235729&partnerID=8YFLogxK
U2 - 10.1155/2019/6438196
DO - 10.1155/2019/6438196
M3 - Journal article
C2 - 30733648
SN - 1555-4309
VL - 2019
SP - 1
EP - 7
JO - Contrast Media and Molecular Imaging
JF - Contrast Media and Molecular Imaging
M1 - 6438196
ER -