Optimization of ⁶⁸Ga-lactosylated human serum albumin (LSA) for PET-based quantitative evaluation of hepatic functional reserve in liver fibrosis models.
18 affiliations
- 1Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
- 2Research Institute for Convergence Science, Seoul National University, Seoul, Republic of Korea.
- 3Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.
- 4Department of Nuclear Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
- 5Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, Tx, USA.
- 6Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.
- 7Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
- 8Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
- 9Cellbion Co., Ltd, Seoul, Republic of Korea.
- 10Department of Nuclear Medicine, Korea University College of Medicine, Seoul, Republic of Korea. [email protected].
- 11Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. [email protected].
- 12Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea. [email protected].
- 13Cancer Research Institute, Seoul National University, Seoul, Republic of Korea. [email protected].
- 14Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea. [email protected].
- 15Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. [email protected].
- 16Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea. [email protected].
- 17Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea. [email protected].
- 18Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. [email protected].
Abstract
Accurate preoperative assessment of hepatic functional reserve (HFR) and future remnant liver function is essential for reducing postoperative morbidity and mortality after liver surgery, yet current clinical methods remain indirect and provide limited spatial and quantitative information. Here, we developed an asialoglycoprotein receptor (ASGPR)-targeted tracer for positron emission tomography (PET), [⁶⁸Ga]Ga-NOTA-lactosylated human serum albumin ([⁶⁸Ga]Ga-NOTA-LSA), and systematically optimized the degree of lactosylation for hepatic imaging. Comparative evaluation of lactosylated human serum albumin constructs bearing 7 or 12 lactose moieties [LSA (7) and LSA (12)] identified LSA (12) as the preferred construct with more favorable hepatocyte targeting in vivo. [⁶⁸Ga]Ga-NOTA-LSA was radiolabeled with high efficiency within 10 min at room temperature and showed favorable radiochemical stability in phosphate-buffered saline and serum. The optimized precursor was further formulated as a lyophilized kit, enabling rapid one-step ⁶⁸Ga labeling, reproducible preparation, and storage stability. In thioacetamide-induced rat liver fibrosis models, including untreated, spontaneous recovery, and pirfenidone-treated groups, [⁶⁸Ga]Ga-NOTA-LSA PET/CT enabled single-time-point quantitative assessment of hepatic function, with 60 min post-injection selected as the optimal imaging time point. Hepatic uptake and liver-to-heart ratios were markedly reduced in fibrotic livers and progressively restored in recovery and treatment models. PET-derived parameters correlated with histological fibrosis, ASGPR expression, fibrogenic and apoptotic markers, and serum liver injury biomarkers. In contrast, 99mTc-mebrofenin required serial imaging to evaluate hepatobiliary kinetics, highlighting mechanistic and workflow differences between transport-based scintigraphy and receptor-associated PET uptake imaging. Reduced hepatic uptake was also reproduced in a fibrotic mouse model. In addition, single-dose toxicity testing showed favorable acute tolerability of non-radioactive NOTA-LSA. Together, these findings support the feasibility of [⁶⁸Ga]Ga-NOTA-LSA as a reproducible and quantitative PET platform for HFR imaging with translational potential.
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BibTeX
@article{park2026optimization,
title = {{Optimization of ⁶⁸Ga-lactosylated human serum albumin (LSA) for PET-based quantitative evaluation of hepatic functional reserve in liver fibrosis models.}},
author = {Boeun Park and Ji Yong Park and Kisoo Pahk and Jin Sil Kim and Chanmin Joung and Jung Woo Byun and Ran Ji Yoo and Ji Seon Mun and Kyungsil Chae and Jae Min Jeong and Sungeun Kim and Jin Chul Paeng and Yun-Sang Lee},
journal = {Journal of nanobiotechnology},
year = {2026},
month = jul,
doi = {10.1186/s12951-026-04827-y},
url = {https://europepmc.org/article/MED/42902275},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Optimization of ⁶⁸Ga-lactosylated human serum albumin (LSA) for PET-based quantitative evaluation of hepatic functional reserve in liver fibrosis models.
AU - Boeun Park
AU - Ji Yong Park
AU - Kisoo Pahk
AU - Jin Sil Kim
AU - Chanmin Joung
AU - Jung Woo Byun
AU - Ran Ji Yoo
AU - Ji Seon Mun
AU - Kyungsil Chae
AU - Jae Min Jeong
AU - Sungeun Kim
AU - Jin Chul Paeng
AU - Yun-Sang Lee
PY - 2026
DA - 2026/07/01
JO - Journal of nanobiotechnology
DO - 10.1186/s12951-026-04827-y
UR - https://europepmc.org/article/MED/42902275
AB - Accurate preoperative assessment of hepatic functional reserve (HFR) and future remnant liver function is essential for reducing postoperative morbidity and mortality after liver surgery, yet current clinical methods remain indirect and provide limited spatial and quantitative information. Here, we developed an asialoglycoprotein receptor (ASGPR)-targeted tracer for positron emission tomography (PET), [⁶⁸Ga]Ga-NOTA-lactosylated human serum albumin ([⁶⁸Ga]Ga-NOTA-LSA), and systematically optimized the degree of lactosylation for hepatic imaging. Comparative evaluation of lactosylated human serum albumin constructs bearing 7 or 12 lactose moieties [LSA (7) and LSA (12)] identified LSA (12) as the preferred construct with more favorable hepatocyte targeting in vivo. [⁶⁸Ga]Ga-NOTA-LSA was radiolabeled with high efficiency within 10 min at room temperature and showed favorable radiochemical stability in phosphate-buffered saline and serum. The optimized precursor was further formulated as a lyophilized kit, enabling rapid one-step ⁶⁸Ga labeling, reproducible preparation, and storage stability. In thioacetamide-induced rat liver fibrosis models, including untreated, spontaneous recovery, and pirfenidone-treated groups, [⁶⁸Ga]Ga-NOTA-LSA PET/CT enabled single-time-point quantitative assessment of hepatic function, with 60 min post-injection selected as the optimal imaging time point. Hepatic uptake and liver-to-heart ratios were markedly reduced in fibrotic livers and progressively restored in recovery and treatment models. PET-derived parameters correlated with histological fibrosis, ASGPR expression, fibrogenic and apoptotic markers, and serum liver injury biomarkers. In contrast, 99mTc-mebrofenin required serial imaging to evaluate hepatobiliary kinetics, highlighting mechanistic and workflow differences between transport-based scintigraphy and receptor-associated PET uptake imaging. Reduced hepatic uptake was also reproduced in a fibrotic mouse model. In addition, single-dose toxicity testing showed favorable acute tolerability of non-radioactive NOTA-LSA. Together, these findings support the feasibility of [⁶⁸Ga]Ga-NOTA-LSA as a reproducible and quantitative PET platform for HFR imaging with translational potential.
SN - 1477-3155
ER -