Peptide-Derived [⁶⁸Ga]Ga-SMIC-1014 for c‑Met-Targeted Tumor PET Imaging: Preclinical and Pilot Clinical Studies.
4 affiliations
- 1PET Center, Department of Nuclear Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510515, China.
- 2State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China.
- 3Department of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510515, China.
- 4Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510515, China.
Abstract
As the mesenchymal-epithelial transition factor (c-Met) is a crucial therapeutic target for multiple malignancies, we previously developed a c-Met-targeted peptide-based positron emission tomography (PET) probe, [68Ga]-Ga-SMIC-1014, derived from the Kringle 3 (K3) domain of hepatocyte growth factor (HGF). Given tumor heterogeneity, this study sought to further validate the preclinical performance of [68Ga]-Ga-SMIC-1014 and evaluate its clinical value in cancer patients. [68Ga]-Ga-SMIC-1014 was successfully synthesized with high radiochemical yield (>80%, non-decay corrected) and purity (>99%), and favorable in vitro stability in PBS and FBS. In vitro cellular uptake of the probe was positively correlated with c-Met expression levels in tumor cells, as verified by Western blot analysis. Small-animal PET and biodistribution studies demonstrated that [68Ga]-Ga-SMIC-1014 exhibited significantly higher tumor accumulation in mouse models with high c-Met expression than those with low c-Met expression (1.92 ± 0.12 vs. 0.49 ± 0.07 %ID/g at 60 min post-injection). Blocking studies with unlabeled SMIC-1014 verified the specific c-Met binding of [68Ga]-Ga-SMIC-1014 both in vitro and in vivo. The probe displayed good safety in human subjects, with physiological renal excretion and minimal-to-mild uptake in normal organs. Tumor uptake of [68Ga]-Ga-SMIC-1014 correlated well with c-Met expression levels in lung cancer patients. Collectively, [68Ga]-Ga-SMIC-1014 is safe and well tolerated in human subjects, and correlates with tumor c-Met expression, supporting its potential as a PET probe for imaging c-Met-positive tumors.
Related
- Glial Scar-Targeted Modification of Hepatocyte Growth Factor-Derived Peptide for Spinal Cord Injury Therapeutic Repair.
- Therapeutic potential of umbilical cord-derived MSCs in arthritis: Insights from preclinical and clinical studies
- Molecular imaging tracers targeting c-MET: a systematic review of preclinical evidence and clinical translation
- A Randomized Clinical Trial of a Standardized Pumpkin-Seed-Derived Peptide Extract: Body Composition Outcomes and Exploratory Analysis by Baseline Adiposity in Overweight Adults
- 224 Preclinical evaluation of a claudin18.2-sensing, membrane-proximal mesothelin-targeted SNIPR CAR-T platform for pancreatic cancer and other solid tumors
BibTeX
@article{guo2026peptidederived,
title = {{Peptide-Derived [⁶⁸Ga]Ga-SMIC-1014 for c‑Met-Targeted Tumor PET Imaging: Preclinical and Pilot Clinical Studies.}},
author = {Danyi Guo and Yang Chen and Zican Feng and Renli Luo and Baozhen Zeng and Yinting Hu and Zhenxiang Li and Zhen Cheng and Dan Tian and Lei Jiang},
journal = {Chemical \& biomedical imaging},
year = {2026},
month = sep,
doi = {10.1021/cbmi.6c00141},
url = {https://europepmc.org/article/MED/42953704},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Peptide-Derived [⁶⁸Ga]Ga-SMIC-1014 for c‑Met-Targeted Tumor PET Imaging: Preclinical and Pilot Clinical Studies.
AU - Danyi Guo
AU - Yang Chen
AU - Zican Feng
AU - Renli Luo
AU - Baozhen Zeng
AU - Yinting Hu
AU - Zhenxiang Li
AU - Zhen Cheng
AU - Dan Tian
AU - Lei Jiang
PY - 2026
DA - 2026/09/07
JO - Chemical & biomedical imaging
DO - 10.1021/cbmi.6c00141
UR - https://europepmc.org/article/MED/42953704
AB - As the mesenchymal-epithelial transition factor (c-Met) is a crucial therapeutic target for multiple malignancies, we previously developed a c-Met-targeted peptide-based positron emission tomography (PET) probe, [68Ga]-Ga-SMIC-1014, derived from the Kringle 3 (K3) domain of hepatocyte growth factor (HGF). Given tumor heterogeneity, this study sought to further validate the preclinical performance of [68Ga]-Ga-SMIC-1014 and evaluate its clinical value in cancer patients. [68Ga]-Ga-SMIC-1014 was successfully synthesized with high radiochemical yield (>80%, non-decay corrected) and purity (>99%), and favorable in vitro stability in PBS and FBS. In vitro cellular uptake of the probe was positively correlated with c-Met expression levels in tumor cells, as verified by Western blot analysis. Small-animal PET and biodistribution studies demonstrated that [68Ga]-Ga-SMIC-1014 exhibited significantly higher tumor accumulation in mouse models with high c-Met expression than those with low c-Met expression (1.92 ± 0.12 vs. 0.49 ± 0.07 %ID/g at 60 min post-injection). Blocking studies with unlabeled SMIC-1014 verified the specific c-Met binding of [68Ga]-Ga-SMIC-1014 both in vitro and in vivo. The probe displayed good safety in human subjects, with physiological renal excretion and minimal-to-mild uptake in normal organs. Tumor uptake of [68Ga]-Ga-SMIC-1014 correlated well with c-Met expression levels in lung cancer patients. Collectively, [68Ga]-Ga-SMIC-1014 is safe and well tolerated in human subjects, and correlates with tumor c-Met expression, supporting its potential as a PET probe for imaging c-Met-positive tumors.
SN - 2832-3637
ER -