A Breakthrough Theranostic Approach Against Pancreatic Cancer

Summary:

Researchers at Osaka University have developed an innovative theranostic strategy that both detects and treats pancreatic cancer. By radioactively labeling a monoclonal antibody targeting glypican-1 (GPC1)—a protein highly expressed in pancreatic tumors—the team demonstrated that one isotope, ⁸⁹Zr, enables early cancer detection via PET imaging, while another isotope, ²¹¹At, delivers targeted alpha therapy to slow tumor growth.

FULL STORY

Pancreatic ductal adenocarcinoma (PDAC) remains one of the world’s deadliest cancers, with a five-year survival rate below 10%. Early detection is notoriously difficult, as most PDAC tumors go unnoticed using conventional imaging tools, including standard fluorodeoxyglucose (FDG) PET scans.

To tackle this challenge, a team led by Osaka University scientists has pioneered a dual-function method that merges diagnosis and therapy into a single process known as theranostics—short for “therapy” and “diagnostics.”

In a study published in the Journal of Nuclear Medicine, the researchers introduced a radio-theranostic approach using a monoclonal antibody (mAb) that specifically targets glypican-1 (GPC1), a cell surface protein that is abundantly expressed in PDAC tumors but minimally present in normal tissues.

“We decided to target GPC1 because it’s overexpressed in pancreatic cancer but occurs only in trace amounts in healthy tissues,” explains Dr. Tadashi Watabe, lead author of the study.

Dual Radiolabeling for Diagnosis and Treatment

The team engineered the GPC1-targeting antibody to carry two different radioactive isotopes—⁸⁹Zr (zirconium-89) for diagnostic PET imaging and ²¹¹At (astatine-211) for therapeutic alpha-particle emission.

Using a xenograft mouse model implanted with human pancreatic cancer cells, the researchers administered both radiolabeled antibodies intravenously to evaluate their diagnostic and therapeutic capabilities.

“We tracked the uptake of ⁸⁹Zr-GPC1 mAb for seven days using PET imaging,” explains Dr. Kazuya Kabayama, co-author of the study. “The strong accumulation of the antibody in tumors indicated precise tumor visualization. When GPC1 expression was knocked out, uptake dropped sharply, confirming that binding was GPC1-specific.”

Targeted Alpha Therapy Significantly Slows Tumor Growth

To test the therapeutic potential, the team used ²¹¹At-GPC1 mAb for alpha therapy—a form of treatment that emits high-energy alpha particles capable of destroying cancer cells at close range.

This treatment induced DNA double-strand breaks in pancreatic tumor cells and led to significant suppression of tumor growth. Control experiments showed that these effects did not occur when the antibody’s internalization was blocked, nor when non-radiolabeled GPC1 antibodies were used.

“Both radiolabeled forms of GPC1 mAb produced promising results,” says Watabe. “⁸⁹Zr-GPC1 mAb demonstrated high tumor targeting for imaging, while ²¹¹At-GPC1 mAb effectively slowed PDAC progression through targeted alpha therapy.”

Toward Early Detection and Personalized Treatment

This pioneering work highlights the potential of radio-theranostics to revolutionize the management of pancreatic ductal adenocarcinoma—enabling early detection through imaging and precision therapy using the same molecular target.

If validated in future clinical studies, this dual approach could pave the way for personalized medicine in pancreatic cancer, a disease that urgently needs more effective diagnostic and therapeutic tools.

Reference

Journal of Nuclear Medicine

Tadashi Watabe, Kazuya Kabayama, Sadahiro Naka, Ryuku Yamamoto, Kazuko Kaneda, Satoshi Serada, Kazuhiro Ooe, Atsushi Toyoshima, Yang Wang, Hiromitsu Haba, Kenta Kurimoto, Takanori Kobayashi, Eku Shimosegawa, Noriyuki Tomiyama, Koichi Fukase, Tetsuji Naka.

Immuno-PET and Targeted α-Therapy Using Anti–Glypican-1 Antibody Labeled with ⁸⁹Zr or ²¹¹At: A Theranostic Approach for Pancreatic Ductal Adenocarcinoma.

Journal of Nuclear Medicine, 2023 — DOI: 10.2967/jnumed.123.266313