Multimodal Radiobioconjugates of Magnetic Nanoparticles Labeled with 44Sc and 47Sc for Theranostic Application

Abstract

This study was performed to synthesize multimodal radiopharmaceutical designed for the diagnosis and treatment of prostate cancer. To achieve this goal, superparamagnetic iron oxide (SPIO) nanoparticles were used as a platform for targeting molecule (PSMA-617) and for complexation of two scandium radionuclides, 44Sc for PET imaging and 47Sc for radionuclide therapy. TEM and XPS images showed that the Fe3O4 NPs have a uniform cubic shape and a size from 38 to 50 nm. The Fe3O4 core are surrounded by SiO2 and an organic layer. The saturation magnetization of the SPION core was 60 emu/g. However, coating the SPIONs with silica and polyglycerol reduces the magnetization significantly. The obtained bioconjugates were labeled with 44Sc and 47Sc, with a yield higher than 97%. The radiobioconjugate exhibited high affinity and cytotoxicity toward the human prostate cancer LNCaP (PSMA+) cell line, much higher than for PC-3 (PSMA-) cells. High cytotoxicity of the radiobioconjugate was confirmed by radiotoxicity studies on LNCaP 3D spheroids. In addition, the magnetic properties of the radiobioconjugate should allow for its use in guide drug delivery driven by magnetic field gradient.

Multi-Modal Laser-Fabricated Nanocomposites with Non-Invasive Tracking Modality and Tuned Plasmonic Properties

“…Another point can be related to the development of nanoparticle-based carriers of radionuclides (RNs) for biomedical applications. Until now, they were usually prepared via different complex methods and successfully assessed for different theranostic applications including cancer therapy [49][50][51][52][53]. The aforementioned laser-based technology can be a new promising approach used for the development and easy synthesis of nanoparticle radiocarriers in chemically pure conditions.…”

Towards Clinical Development of Scandium Radioisotope Complexes for Use in Nuclear Medicine: Encouraging Prospects with the Chelator 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTA) and Its Analogues

“…Several chelating agents for scandium have been described in the literature in addition to the commonly used DOTA [135][136][137][138][139][140][141][142][143][144][145][146] (Table 4), many of which constitute derivatives or structural analogues of DOTA, with the same (DO3AP, DO3AP PrA , DO3AP ABn , DO3AM-NI, NBD), smaller (H3mpatcn, NOTA, AAZTA), or larger (TETA) macrocyclic ring system, while others are non-cyclic counterparts (EDTA, DTPA, H4pypa). Note: The IUPAC names of all chelators included in this table can be found in the "Abbreviations" section.…”

“… Representative examples ( A – G ) of Sc-radiolabeled conjugates between a metal chelator (blue) bound to scandium (Sc) and a targeting moiety (peptide or peptide-like small molecule, maroon). Some of these conjugates have been successfully used in vivo for delivering radionuclides to tumors, for imaging (Sc-44) or therapy (Sc-47) [ 63 , 140 , 141 , 156 , 159 , 160 , 162 ]. (Note: the chelator IUPAC names can be found in the “Abbreviations” section).…”

Three-Dimensional In Vitro Tumor Spheroid Models for Evaluation of Anticancer Therapy: Recent Updates

“…Magnetic nanoparticles (NPs) can be used in nuclear medicine to diagnose and treat [72][73][74]. Unak et al [75] used superparamagnetic iron oxide (SPION) NPs labeled with two scandium radionuclides, 44 Sc and 47 Sc, for detecting and treating prostate cancer. A 3D spheroid model has been developed using the LNCaP (PSMA+) and PC-3 (PSMA−) prostate cancer cell lines.…”