Localization and Tumor Growth Inhibition of I-131-Labeled Monoclonal Antibody ERIC1 in a Subcutaneous Xenograft Model of Small Cell Lung Cancer in SCID Mice

• Published in: International journal of molecular sciences Vol. 25; no. 19; p. 10638
• Main Authors: Fischer, Thomas, Dietrich, Christopher, Dietlein, Felix, Muñoz Vázquez, Sergio, Zimmermanns, Beate, Krapf, Philipp, Sudbrock, Ferdinand, Drzezga, Alexander, Dietlein, Markus, Schomäcker, Klaus
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2024; MDPI
• Subjects: Animals; anti-NCAM antibody; Antibodies; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; biokinetics; Brain cancer; Cancer therapies; Cell Line, Tumor; Chemotherapy; Cytotoxicity; Dosage and administration; Drug therapy; ERIC1; Female; Humans; Iodine Radioisotopes; Lung cancer; Lung cancer, Small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical prognosis; Mice; Mice, SCID; Monoclonal antibodies; Neuroblastoma; Nuclear medicine; Physiological aspects; Precision medicine; Radiation; Remission (Medicine); SCLC; Small Cell Lung Carcinoma - drug therapy; Small Cell Lung Carcinoma - metabolism; Small Cell Lung Carcinoma - pathology; theranostics; Thyroid gland; Tissue Distribution; Tomography; Tumors; Xenograft Model Antitumor Assays; Germany; SCLC; I-131; nuclear medicine; anti-NCAM antibody; ERIC1; tumor growth inhibition; theranostics; biokinetics; mice
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251910638

This study evaluates the efficacy of [ I]I-ERIC1 in targeting and inhibiting the growth of SCLC tumors in mice, focusing on tumor accumulation and regression and potential side effects. NCAM-positive NCI-H69 SCLC cells were implanted in CB 17 SCID mice, and [ I]I-ERIC1 biokinetics were measured in organs and tissues at four post-injection time points (24, 72, 96, and 120 h). The experimental series compared tumor growth, survival, and changes in blood counts among three treatment groups (1, 2, or 3 MBq) and a control group, with treatments initiated either two or five days post implantation. [ I]I-ERIC1 was synthesized with >95% radiochemical purity and a specific activity of 15 TBq/mmol. Tumor activity peaked at 31.5 ± 6.6% ID/g after four days, demonstrating significant antitumor efficacy, which resulted in sustained remission and extended survival. Hematological toxicity was observed, with the optimal dose identified as 2 MBq per animal administered two days post implantation. [ I]I-ERIC1 shows promise as a theranostic agent for personalized cancer treatment by effectively targeting SCLC tumors with manageable side effects. However, further studies are required to optimize dosing strategies and minimize toxicity.