¹⁷⁷Lu Anti-Angiogenic Radioimmunotherapy Targeting ATP Synthase in Gastric Cancer Model

Area of Science:

• Nuclear Medicine
• Oncology
• Immunotherapy

Background:

• Tumor angiogenesis is crucial for cancer growth and metastasis.
• Targeting tumor vasculature offers a therapeutic strategy.
• Adenosine triphosphate synthase (ATPS) is a potential target in cancer cells.

Purpose of the Study:

• To develop and evaluate a novel radioimmunotherapy agent targeting tumor angiogenesis.
• To assess the efficacy of ¹⁷⁷Lu-DOTA-ATPS mAb in preclinical cancer models.
• To investigate the combination therapy of ¹⁷⁷Lu-DOTA-ATPS mAb with sunitinib.

Main Methods:

• Development of a radiopharmaceutical by labeling anti-ATPS monoclonal antibody (mAb) with ¹⁷⁷Lu using DOTA.
• In vitro studies using MKN-45 cancer cells to assess cellular uptake and specificity.
• In vivo studies in a mouse xenograft tumor model to evaluate tumor accumulation and therapeutic efficacy.

Main Results:

• ¹⁷⁷Lu-DOTA-ATPS mAb showed high labeling efficiency (99.0%) and serum stability.
• Significant tumor accumulation of ¹⁷⁷Lu-DOTA-ATPS mAb was observed in mice (16.0 ± 1.5%ID/g at day 7).
• The radioimmunotherapy agent demonstrated dose-dependent reduction in cancer cell viability and 82.8% tumor growth inhibition in vivo. Combination with sunitinib enhanced efficacy.

Conclusions:

• ¹⁷⁷Lu-DOTA-ATPS mAb is a promising radioimmunotherapy agent targeting tumor blood vessels.
• This targeted approach effectively inhibits tumor growth as a single agent or in combination therapies.
• Further development of this strategy holds potential for improved cancer treatment outcomes.