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Characterization and Efficacy of a Nanomedical Radiopharmaceutical for Cancer Treatment

2023.01.04.

Ingrid Yao Mattisson et al, ACS Omega, 2023

Summary

Although much progress has been made over the last decades, there is still a significant clinical need for novel therapies to manage cancer. Typical problems are that solid tumors are frequently inaccessible, aggressive, and metastatic. To contribute to solving some of these issues, we have developed a novel radioisotope-labeled 27 nm nanoparticle, 177Lu-SN201, to selectively target solid tumors via the enhanced permeability and retention effect, allowing irradiation intratumorally. We show that 177Lu-SN201 has robust stealth properties in vitro and anti-tumor efficacy in mouse mammary gland and colon carcinoma models. The possible clinical application is also addressed with single photon emission computed tomography imaging, which confirms uptake in the tumor, with an average activity of 19.4% injected dose per gram (ID/g). The properties of 177Lu-SN201 make it a promising new agent for radionuclide therapy with the potential to target several solid tumor types.

Results from nanoScan® SPECT/CT

  • SPECT images provided insights into the time-dependent uptake and clearance of a novel radioisotope-labelled nanoparticle (177Lu-SN201). The data showed that the nanoparticles were rapidly taken up by tumors shortly after administration and retained within the tumor tissue over time, while showing gradual clearance from non-target areas (Figure 3B).
  • The observed tumor uptake patterns were consistent with the Enhanced Permeability and Retention (EPR) effect, where nanoparticles passively accumulate in tumors, further validating the design and function of the radiopharmaceutical.
  • The authors observed significant accumulation of 177Lu-SN201 within the tumor sites, confirming the nanoparticle's ability to effectively target cancerous tissues (Figure 5C).
    This targeted accumulation was markedly higher compared to non-targeted areas, demonstrating the specificity of the radiopharmaceutical.

Mice treated with 177Lu-SN201 showed a reduced tumor growth rate without signs of radiotoxicity. The best-fit values of tumor doubling time were 11 days for the 177Lu-SN201-treated and 6 days for the vehicle-treated group (p < 0.05) (Figure 5A).

Figure 5. Anti-tumor efficacy and SPECT/CT imaging of 177Lu-SN201. (A) Mean body weight ± SD and (B) relative tumor volume in MC38 tumor-bearing mice after treatment with 4 MBq/mouse (n = 18) 177Lu-SN201 vs vehicle (n = 10). (C) Representative SPECT/CT images of maximum intensity projection and tumor region of interest (ROI) definitions in the coronal, sagittal, and transverse view, 72 h post-treatment with 4 MBq 177Lu-SN201 in MC38 tumor-bearing mouse. The graph presents % ID/g in the ROIs, where bars show the mean ± SD error from n = 3 representative animals per timepoint. Arrows; orange, tumor; green, liver; and blue, spleen.

  • Results show anti-tumor efficacy with a slower tumor growth rate and prolonged survival time significantly in tumor-bearing mouse models of aggressive breast cancer and colon adenocarcinoma.
  • A dose of 4 MBq per mouse resulted in acceptable toxicity and clinically relevant SPECT imaging, indicating that 177Lu-SN201 is a new, promising candidate drug for physiologically targeted radiotherapy of solid tumors.

Full article on pubs.acs.org

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