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Peer-reviewedCC BY-NC-ND 4.0ACS Omega

177Lu-Labeled Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 Monoclonal Antibody-Targeted Therapy for Clear Cell Renal Cell Carcinoma

  • Huiwen Luo1
  • Jianjun Wang2
  • Yuan Cao2
  • Xianfu Cai2
  • Zhou Lu2
  • Yuanyuan Liang2
  • Decai Wang2
  • Xiaoan Li2
  • Xirui Lu1
  1. 1Southwest University of Science and Technology , , , ,
  2. 2University of Electronic Science and Technology of China , , , ,
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Abstract

Clear cell renal cell carcinoma (ccRCC) remains a therapeutic challenge. Ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) is highly expressed in ccRCC tissues and cell lines, representing a promising target. This study aimed to conjugate lutetium-177 (177Lu) to an anti-human ENPP3 monoclonal antibody using tetra-azacyclododecanetetra-acetic acid (DOTA), creating the radioimmunoconjugate [177Lu]Lu-DOTA-ENPP3, and to evaluate its therapeutic effect in ccRCC. The characteristics and effects of [177Lu]Lu-DOTA-ENPP3 were evaluated using in vitro and vivo experiments. [177Lu]Lu-DOTA-ENPP3 exhibited high radiolabeling efficiency and affinity and good stability, specificity, binding, and internalization efficiency. It specifically accumulated at tumor sites. A 12 MBq dose significantly inhibited tumor growth and cell proliferation, without causing significant weight loss or damage to major organs. Therefore, [177Lu]Lu-DOTA-ENPP3 demonstrated good tumor specificity, significant antitumor activity, and favorable safety in treating ccRCC. Dosimetric analyses further quantified radiation exposure to tumors and major normal tissues and provided preliminary human dosimetry estimates. The study’s findings could help treat ccRCC.

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Cite

BibTeXRIS
BibTeX
@article{luo2026177lulabeled,
  title = {{177Lu-Labeled Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 Monoclonal Antibody-Targeted Therapy for Clear Cell Renal Cell Carcinoma}},
  author = {Huiwen Luo and Jianjun Wang and Yuan Cao and Xianfu Cai and Zhou Lu and Yuanyuan Liang and Decai Wang and Xiaoan Li and Xirui Lu},
  journal = {ACS Omega},
  year = {2026},
  month = oct,
  doi = {10.1021/acsomega.6c08024},
  url = {https://pubs.acs.org/acsodf/article/11/41/63768/5444943/177Lu-Labeled-Ectonucleotide-Pyrophosphatase},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - 177Lu-Labeled Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 Monoclonal Antibody-Targeted Therapy for Clear Cell Renal Cell Carcinoma
AU  - Huiwen Luo
AU  - Jianjun Wang
AU  - Yuan Cao
AU  - Xianfu Cai
AU  - Zhou Lu
AU  - Yuanyuan Liang
AU  - Decai Wang
AU  - Xiaoan Li
AU  - Xirui Lu
PY  - 2026
DA  - 2026/10/06
JO  - ACS Omega
DO  - 10.1021/acsomega.6c08024
UR  - https://pubs.acs.org/acsodf/article/11/41/63768/5444943/177Lu-Labeled-Ectonucleotide-Pyrophosphatase
AB  - Clear cell renal cell carcinoma (ccRCC) remains a therapeutic challenge. Ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) is highly expressed in ccRCC tissues and cell lines, representing a promising target. This study aimed to conjugate lutetium-177 (177Lu) to an anti-human ENPP3 monoclonal antibody using tetra-azacyclododecanetetra-acetic acid (DOTA), creating the radioimmunoconjugate [177Lu]Lu-DOTA-ENPP3, and to evaluate its therapeutic effect in ccRCC. The characteristics and effects of [177Lu]Lu-DOTA-ENPP3 were evaluated using in vitro and vivo experiments. [177Lu]Lu-DOTA-ENPP3 exhibited high radiolabeling efficiency and affinity and good stability, specificity, binding, and internalization efficiency. It specifically accumulated at tumor sites. A 12 MBq dose significantly inhibited tumor growth and cell proliferation, without causing significant weight loss or damage to major organs. Therefore, [177Lu]Lu-DOTA-ENPP3 demonstrated good tumor specificity, significant antitumor activity, and favorable safety in treating ccRCC. Dosimetric analyses further quantified radiation exposure to tumors and major normal tissues and provided preliminary human dosimetry estimates. The study’s findings could help treat ccRCC.
SN  - 2470-1343
ER  -