Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 20;12(14):2490.
doi: 10.3390/nano12142490.

Preliminary Evaluation of Iron Oxide Nanoparticles Radiolabeled with 68Ga and 177Lu as Potential Theranostic Agents

Evangelia-Alexandra Salvanou  1   2 , Argiris Kolokithas-Ntoukas  2 , Christos Liolios  1   3 , Stavros Xanthopoulos  1 , Maria Paravatou-Petsotas  1 , Charalampos Tsoukalas  1 , Konstantinos Avgoustakis  2 , Penelope Bouziotis  1
Affiliations

Preliminary Evaluation of Iron Oxide Nanoparticles Radiolabeled with 68Ga and 177Lu as Potential Theranostic Agents

Evangelia-Alexandra Salvanou et al. Nanomaterials (Basel). .

Abstract

Theranostic radioisotope pairs such as Gallium-68 (68Ga) for Positron Emission Tomography (PET) and Lutetium-177 (177Lu) for radioisotopic therapy, in conjunction with nanoparticles (NPs), are an emerging field in the treatment of cancer. The present work aims to demonstrate the ability of condensed colloidal nanocrystal clusters (co-CNCs) comprised of iron oxide nanoparticles, coated with alginic acid (MA) and stabilized by a layer of polyethylene glycol (MAPEG) to be directly radiolabeled with 68Ga and its therapeutic analog 177Lu. 68Ga/177Lu- MA and MAPEG were investigated for their in vitro stability. The biocompatibility of the non-radiolabeled nanoparticles, as well as the cytotoxicity of MA, MAPEG, and [177Lu]Lu-MAPEG were assessed on 4T1 cells. Finally, the ex vivo biodistribution of the 68Ga-labeled NPs as well as [177Lu]Lu-MAPEG was investigated in normal mice. Radiolabeling with both radioisotopes took place via a simple and direct labelling method without further purification. Hemocompatibility was verified for both NPs, while MTT studies demonstrated the non-cytotoxic profile of the nanocarriers and the dose-dependent toxicity for [177Lu]Lu-MAPEG. The radiolabeled nanoparticles mainly accumulated in RES organs. Based on our preliminary results, we conclude that MAPEG could be further investigated as a theranostic agent for PET diagnosis and therapy of cancer.

Keywords: Gallium-68; Lutetium-177; MTT; biodistribution; condensed clusters; in vivo tracking; iron oxide nanoparticles; radiolabeling.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 9
Figure 9
MTT assay of MA against the 4T1 cell line after 24, 48, and 72 h. Mean values (n = 3) and the SD (bars) are shown (x axis not in scale).
Figure 10
Figure 10
MTT assay of MAPEG against the 4T1 cell line after 24, 48 and 72 h. Mean values (n = 3) and the SD (bars) are shown (x axis not in scale).
Figure 11
Figure 11
MTT assay of [177Lu]Lu-MAPEG against the 4T1 cell line after 24 h. Mean values (n = 3) and the SD (bars) are shown (x axis not in scale).
Figure 1
Figure 1
(a) Hydrodynamic diameters (Dh’s) and (b) ζ-potentials of the plain (MA) and PEGylated (MAPEG) co-CNCs MIONs.
Figure 2
Figure 2
Representative radio-TLC chromatograph of [68Ga]Ga-MA or [68Ga]Ga-MAPEG obtained after 30 min of incubation at 75 °C.
Figure 3
Figure 3
Size distribution of MIONs before (MAPEG) and after (68Ga-MAPEG) radiolabeling with 68Ga.
Figure 4
Figure 4
Radiochemical stability of [68Ga]Ga-MA and [68Ga]Ga-MAPEG at RT and in human serum (x axis not in scale).
Figure 5
Figure 5
Representative radio-TLC chromatograph of [177Lu]Lu-MA or [177Lu]Lu-MAPEG after 30 min of incubation at 75 °C.
Figure 6
Figure 6
Size distribution of MIONs before (MAPEG) and after (177Lu-MAPEG) radiolabeling with 177Lu.
Figure 7
Figure 7
Radiochemical stability of [177Lu]Lu-MA and [177Lu]Lu-MAPEG at RT and in human serum (x axis not in scale).
Figure 8
Figure 8
Hemolytic effect of different concentrations of MA and MAPEG. Positive control: 500 μL H2O + 15 μL of RBCs; negative control: 500 μL PBS + 15 μL of RBCs.
Figure 12
Figure 12
Biodistribution of [68Ga]Ga-MA in normal mice expressed as % IA/g (n = 3).
Figure 13
Figure 13
Biodistribution of [68Ga]Ga-MAPEG in normal mice expressed as % IA/g (n = 3).
Figure 14
Figure 14
Biodistribution of [177Lu]Lu-MAPEG in normal mice expressed as % IA/g (n = 3).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Same S., Aghanejad A., Akbari Nakhjavani S., Barar J., Omidi Y. Radiolabeled Theranostics: Magnetic and Gold Nanoparticles. Bioimpacts. 2016;6:169–181. doi: 10.15171/bi.2016.23. - DOI - PMC - PubMed
    1. Singh R., Lillard J.W. Nanoparticle-Based Targeted Drug Delivery. Exp. Mol. Pathol. 2009;86:215–223. doi: 10.1016/j.yexmp.2008.12.004. - DOI - PMC - PubMed
    1. Gurunathan S., Kang M.-H., Qasim M., Kim J.-H. Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer. Int. J. Mol. Sci. 2018;19:3264. doi: 10.3390/ijms19103264. - DOI - PMC - PubMed
    1. Hamoudeh M., Kamleh M.A., Diab R., Fessi H. Radionuclides Delivery Systems for Nuclear Imaging and Radiotherapy of Cancer. Adv. Drug Deliv. Rev. 2008;60:1329–1346. doi: 10.1016/j.addr.2008.04.013. - DOI - PubMed
    1. Montiel Schneider M.G., Martín M.J., Otarola J., Vakarelska E., Simeonov V., Lassalle V., Nedyalkova M. Biomedical Applications of Iron Oxide Nanoparticles: Current Insights Progress and Perspectives. Pharmaceutics. 2022;14:204. doi: 10.3390/pharmaceutics14010204. - DOI - PMC - PubMed

LinkOut - more resources