TY - JOUR
T1 - Development of 68Ga-labeled tin colloids for evaluating phagocytic function of Kupffer cells using preclinical PET imaging
AU - Matsusaka, Yoji
AU - Nakahara, Tadaki
AU - Takahashi, Kazuhiro
AU - Iwabuchi, Yu
AU - Nakamura, Shoki
AU - Jinzaki, Masahiro
N1 - Funding Information:
This research was supported by JSPS KAKENHI (Grant no. JP18K07689). Acknowledgements
Funding Information:
We thank the Department of Radiology staff at Research Institute of Brain and Blood Vessels-Akita for supplying the 68 Ge/ 68 Ga generator, and the Radiation Safety Office staff at the Hospital and School of Medicine in Keio University for setting the experimental environment. We would like to thank Editage (http://www.editage.com ) for English language editing.
Funding Information:
TN and MJ received research grants from Nihon Medi-Physics Co., Ltd. and GE Healthcare Corp. All other authors declare no conflicts of interest.
Publisher Copyright:
© 2020, The Japanese Society of Nuclear Medicine.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Objective: This study aimed to investigate the optimal conditions for producing 68Ga-labeled tin colloid and the feasibility of 68Ga-tin colloid positron emission tomography (PET) for visualization and evaluation of the phagocytic function of Kupffer cells (KCs) in vivo. Methods: 68Ga-tin colloid was prepared by adding tin solution (1 mM, 0.2 mL) to 68Ga solution (1.0 mL), followed by pH adjustment with sodium acetate (1 M, 0.2 mL). Various labeling times were tested to find the optimal one. Colloid size was measured by filtering the solution through three-ply membrane filters (with pore sizes of 200, 3000, and 5000 nm), and radioactivity was measured in the whole filtrate and the filters using a gamma counter. The in vitro stability of the colloid was evaluated by the size measurement after incubation under ambient conditions for up to 60 min. PET scanning was performed for 30 min after intravenous administration of 68Ga-tin colloid solution (4 MBq) to healthy rats. Time-activity-curves for the liver, spleen, and blood pool were generated. Finally, liver uptake was compared before and after the establishment of KC-depletion and non-alcoholic steatohepatitis (NASH) rat models. Results: Colloid size increased with increasing labeling time. After pH adjustment, the colloid sizes remained nearly unchanged. The optimal labeling time was determined as 30 min. PET imaging of healthy rats revealed that liver uptake of the 68Ga-tin colloid increased with increasing colloid size. In KC-depleted rats, liver uptake significantly decreased (n = 4, p < 0.01). NASH model rats showed significantly decreased uptake of 68Ga-tin colloid in the livers (n = 5, p < 0.01). Conclusions: 68Ga-tin colloid, prepared by a simple radiolabeling method, enabled in vivo PET imaging to evaluate the phagocytic function of KCs.
AB - Objective: This study aimed to investigate the optimal conditions for producing 68Ga-labeled tin colloid and the feasibility of 68Ga-tin colloid positron emission tomography (PET) for visualization and evaluation of the phagocytic function of Kupffer cells (KCs) in vivo. Methods: 68Ga-tin colloid was prepared by adding tin solution (1 mM, 0.2 mL) to 68Ga solution (1.0 mL), followed by pH adjustment with sodium acetate (1 M, 0.2 mL). Various labeling times were tested to find the optimal one. Colloid size was measured by filtering the solution through three-ply membrane filters (with pore sizes of 200, 3000, and 5000 nm), and radioactivity was measured in the whole filtrate and the filters using a gamma counter. The in vitro stability of the colloid was evaluated by the size measurement after incubation under ambient conditions for up to 60 min. PET scanning was performed for 30 min after intravenous administration of 68Ga-tin colloid solution (4 MBq) to healthy rats. Time-activity-curves for the liver, spleen, and blood pool were generated. Finally, liver uptake was compared before and after the establishment of KC-depletion and non-alcoholic steatohepatitis (NASH) rat models. Results: Colloid size increased with increasing labeling time. After pH adjustment, the colloid sizes remained nearly unchanged. The optimal labeling time was determined as 30 min. PET imaging of healthy rats revealed that liver uptake of the 68Ga-tin colloid increased with increasing colloid size. In KC-depleted rats, liver uptake significantly decreased (n = 4, p < 0.01). NASH model rats showed significantly decreased uptake of 68Ga-tin colloid in the livers (n = 5, p < 0.01). Conclusions: 68Ga-tin colloid, prepared by a simple radiolabeling method, enabled in vivo PET imaging to evaluate the phagocytic function of KCs.
KW - Ga-labeled tin colloid
KW - Kupffer cells
KW - Phagocytic function
KW - Positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=85088929390&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088929390&partnerID=8YFLogxK
U2 - 10.1007/s12149-020-01505-3
DO - 10.1007/s12149-020-01505-3
M3 - Article
C2 - 32749578
AN - SCOPUS:85088929390
VL - 34
SP - 807
EP - 814
JO - Annals of Nuclear Medicine
JF - Annals of Nuclear Medicine
SN - 0914-7187
IS - 11
ER -