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Preclinical evaluation of an 111In/225Ac theranostic targeting transformed MUC1 for triple negative breast cancer

2020.05.25.

Vanessa J Kelly et al., Theranostics, 2020

Summary

Triple-negative breast cancers (TNBC) are associated with poor prognosis and high mortality rates following relapse. These cells do not express estrogen, progesterone or HER2/neu receptors, which means that receptor targeted therapies can’t be utilized. These cells overexpress transformed MUC1 (tMUC1) antigen, which is selectively bound by murine antibody TAB004. Once TAB004 binds to tMUC1 it has been shown to internalize, which makes them excellent therapeutic candidate for TNBC.

Current study aimed to evaluate humanized TAB004 (hTAB004) as a potential theranostic for TNBC. hTAB004 was labeled either with Indium-111 (for biodistribution analysis) or Actinium-225 (for alpha radiotherapy) and injected intravenously to orthotopic tumor bearing mice. Results demonstrate both high tumor concentrations and high tumor-to-blood ratios. Additionally, a single administration of 225Ac-DOTA-hTAB004 increased survival and resulted in consistently lower tumor volumes compared to the control group after 12 days. Together they are convincing proof-of-concept support for hTAB004 as a theranostic agent in triple negative breast cancer.

 

Results from nanoScan SPECT/CT

In vivo biodistribution studies: NSG mice were inoculated with HCC70 tumors. 27 days later 7.5MBq 111In-DOTAhTAB004 was intravenously injected via the tail vein. SPECT-CT imaging was performed at 4, 24, 48 and 120 h postinjection.

  • The tumor accumulation of 111In-DOTA-hTAB004 increased over 120 h reaching a maximum of 65.4 ± 15.2 %ID/g. All other organs (blood, bone, kidneys, liver, lungs, muscle, pancreas, spleen) had <10% ID/g at this time.

  

  • Efficacy studies: Athymic nude mice were inoculated with HCC70 tumor cells. 27 days later they were injected via the tail vein with either 225Ac-DOTA-hTAB004 (18.5 kBq) or DOTA-hTAB004 and monitored for tumor growth via caliper measurements. The 225Ac-DOTA-hTAB004 group had significantly smaller tumors and greater survival compared to the control group.

Full article on thno.org

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