Targeted radionuclide therapy for non-small cell lung cancer with LU-177 ebrgd

The National Cancer Institute awarded Molecular Targeting Technologies, Inc. $637,529 on August 24, 2026, under the Cancer Detection and Diagnosis Research program (CFDA 93.394) to develop targeted radionuclide therapy for non-small cell lung cancer using Lu-177 EBRGD.

The award funds research to evaluate in vivo tumor targeting, biodistribution, therapeutic efficacy, and normal tissue toxicity of 177Lu-DOTA-EB-RGD as a treatment for non-small cell lung cancer, which accounts for 80–85 percent of all lung cancer cases and is typically diagnosed at advanced stages with five-year survival rates below 10 percent. Prior work demonstrated anti-tumor activity of 177Lu-DOTA-EB-RGD in mouse models of non-small cell lung cancer. The research employs vertebrate animal models to assess performance that cannot be adequately evaluated using in vitro systems alone. This work supports the long-term goal of developing a radionuclide therapy to address an unmet clinical need in non-small cell lung cancer treatment.

Molecular Targeting Technologies, Inc., a for-profit small business, is the recipient. Performance occurs in Pennsylvania. The project period runs through July 31, 2031.

Abstract

Lung cancer is the leading cause of cancer-related death worldwide. The two major forms of lung cancer are non-small cell lung cancer (nsclc) and small cell lung cancer. Nsclc accounts for approximately 80% to 85% of lung cancers, and adenocarcinoma is the most common histologic subtype. Currently, most nsclc patients are diagnosed in advanced stages with five-year survival rates of less than 10%. Chemotherapy based on platinum is the first-line treatment for nsclc but only provides modest survival benefit, especially for the squamous subtype of nsclc. Therefore, a novel therapy is needed to significantly improve patient outcome. Targeted radionuclide therapy (TRT) uses isotope-emitting charged particles coupled to a targeting ligand. Besides being utilized in the treatment of local tumors, TRT can treat metastatic tumors through systemic administration. There are currently two approved 177LU based therapies in the US. 177LU-dotatate is indicated for treating neuroendocrine tumors and 177LU-vipivotide tetraxen for the treatment of metastatic castrationresistant prostate cancer. 90Y-dota-EB-RGD showed impressive anti-tumor activity in u-87 tumor bearing mice. Results of suppressing tumor growth were also observed for 177LU-dota-EB-RGD in mice implanted with MC38 murine colon adenocarcinoma and in a patient derived xenograft mouse model of nsclc. Therefore, the demonstrated significance of 177LU-dota-EB-RGD as a potential TRT agent for nsclc treatment supports further exploration. Vertebrate animal models are essential to evaluate in vivo tumor targeting, biodistribution, therapeutic efficacy, and normal tissue toxicity, which cannot be adequately assessed using in vitro systems alone. An effective treatment for nsclc patients is a critical unmet need. In line with the mission of the national cancer institute, the long-term goal of this proposal is to develop radiolabeled EB-RGD as a potential targeted radionuclide therapeutic agent for nsclc patients. This proposal will attempt to demonstrate that 177LU-dotaeb- RGD can exhibit inhibitory tumor activity in PDX nsclc mouse models, and IT is effective and safe for nsclc patients. Specific aims include: SA1: conduct pre-clinical studies in mice to further validate 177LU-dota-EB-RGD for the evaluation of treatment options in nsclc patients. SA2: manufacture of 177LU-dota-EB-RGD (drug product) in compliance with cgmp. SA3A: IND submission for testing 177LU-dota-EB-RGD in nsclc patients. SA3B: evaluate the clinical usefulness of 177LU-dota-EB-RGD in adult patients with metastatic nsclc who have failed first-line systemic therapy in the setting of a clinical trial.