Current and Future Theranostic Applications of the Lipid-Calcium-Phosphate Nanoparticle Platform

Abstract

Over the last four years, the Lipid-Calcium-Phosphate (LCP) nanoparticle platform has shown success in a wide range of treatment strategies, recently including theranostics. The high specific drug loading of radiometals into LCP, coupled with its ability to efficiently encapsulate many types of cytotoxic agents, allows a broad range of theranostic applications, many of which are yet unexplored. In addition to providing an overview of current medical imaging modalities, this review highlights the current theranostic applications for LCP using SPECT and PET, and discusses potential future uses of the platform by comparing it with both systemically and locally delivered clinical radiotherapy options as well as introducing its applications as an MRI contrast agent. Strengths and weaknesses of LCP and of nanoparticles in general are discussed, as well as caveats regarding the use of fluorescence to determine the accumulation or biodistribution of a probe.

Keywords: Cancer; LCP.; Nanoparticle; PET; SIRT; SPECT; Theranostic.

Figure 1

Schematic of LCP nanoparticle synthesis. LCP is capable of encapsulating siRNA, mRNA, DNA, phosphorylated peptides, nucleotide mimics, and radioactive isotopes in its calcium phosphate core. Source: Adapted from Satterlee et al. Copyright © 2015 Elsevier B.V. License number: 3815560646760

Figure 2

Chemical Structure of the PRRT agent ¹⁷⁷Lu-DOTA-TATE

Figure 3

(A) SPECT/CT and (B) Cerenkov imaging of a live athymic nude mouse bearing a subcutaneous UMUC3/3T3 stroma-rich bladder cancer tumor at t = 24 h after i.v. injection of 2.5 mCi of ¹⁷⁷Lu-LCP. Tumor accumulation of ¹⁷⁷Lu is clearly visible above background, although not as high as liver and spleen accumulation. SPECT and Cerenkov agree on the overall biodistribution of ¹⁷⁷Lu. Source: Adapted from Satterlee et al. Copyright © 2015 Elsevier B.V. License number: 3815560646760

Figure 4

PET (left) and PET/CT (right) images of a live athymic nude mouse bearing a subcutaneous A549 lung cancer tumor. Images show 2-D coronal sections at t = 22h after ⁶⁴Cu-GMP-LCP administration. Liver and tumor accumulation of ⁶⁴Cu are both clearly visible. Dose of ⁶⁴Cu = 500 μCi; dose of GMP = 5 mg/kg.

Figure 5

Biodistribution kinetics in a live athymic nude mouse bearing a subcutaneous A549 lung cancer tumor: (A) Quantification of ⁶⁴Cu from ⁶⁴Cu-GMP-LCP in liver and tumor, calculated from PET reconstruction ROIs; (B) PET images of 2-D transverse liver sections at different time points after injection; (C) PET images of 2-D coronal tumor sections at different time points after injection; (D) 3-D reconstruction of ⁶⁴Cu biodistribution from ⁶⁴Cu-GMP-LCP at different time points after injection. Arrows at 16 h and 22 h time points show accumulation of ⁶⁴Cu in the intestines. Dose of ⁶⁴Cu = 500 μCi; dose of GMP = 5 mg/kg.