Encapsulation of a Radiolabeled Cluster Inside a Fullerene Cage, ¹⁷⁷Lu_xLu_(3−x)N@C₈₀: An Interleukin-13-Conjugated Radiolabeled Metallofullerene Platform

Abstract

In this communication, we describe the successful encapsulation of (177)Lu into the endohedral metallofullerene (177)Lu(x)Lu(3-x)N@C(80) (x = 1-3) starting with (177)LuCl(3) in a modified quartz Kraschmer-Huffman electric generator. We demonstrate that the (177)Lu (beta-emitter) in this fullerene cage is not significantly released for a period of up to at least one-half-life (6.7 days). We also demonstrate that this agent can be conjugated with an interleukin-13 peptide that is designed to target an overexpressed receptor in glioblastoma multiforme tumors. This nanoparticle delivery platform provides flexibility for a wide range of radiotherapeutic and radiodiagnostic multimodal applications.

Efficient Uptake of 177Lu‐Porphyrin‐PEG Nanocomplexes by Tumor Mitochondria for Multimodal‐Imaging‐Guided Combination Therapy

“…[5] Radioisotope 177 Lu has favorably long nuclear decay properties (t 1/2 = 6.65 d) and can be used to easily radiolabel av ariety of molecular carriers. [6] As such, 177 Lu promises to benefit nanoparticle-mediated combination therapy.Previous studies explored 177 Lu-labeled gold nanoparticles for preclinical nuclear medicine. [7] However,t he clinical translation of the reported nanosystem was impeded because of high and long-term accumulation in the reticuloendothelial system (RES) and low intratumor uptake.T hus,i tr emains ab ig challenge to integrate nanocarrier tumor-targeted delivery and multi-modal imaging using 177 Lu to obtain an anotheranostic agent with high efficiacy.…”

Chelating agents for radiolanthanides: Applications to imaging and therapy

“…28). 164 The encapsulated 177 Lu(III) ions were not released for at least one half-life (6.7 177-Lu x Lu 3-x N@C 80 surface functionalisation for solubility, biocompatibility and targeting days) showing the robustness of the system, and the fullerene was surface tagged with an interleukin-13 peptide. The mechanism for the loss of 177 Lu from the cage beyond this timescale has not been postulated, but assumed to proceed via radiolytic damage.…”

Fullerene derivatives as nano-additives in polymer composites

“…For the imaging capabilities of this theranostic agent, see Ref. 327. Regarding therapeutic efficacy in vivo, see Ref.…”

“…346 It was also shown that a conjugate of radiolabelled cluster 177 Lu x Lu (37x) N@C 80 with the 1L-13 peptide and a fluorescent tag (tetramethyl-6-carboxyrhodamine, TAMRA) can be used for radiotherapeutic and radiodiagnostic applications. 327 Endometallofullerenes and chemotherapeutic pharmaceuticals. Anticancer drugs can also be designed on the basis of EMFs containing no radioactive atoms.…”