¹⁷⁷Lu-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize ¹⁷⁷Lu-dendrimer(PAMAM-G4)-folate-bombesin with gold nanoparticles (AuNPs) in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs) and gastrin-releasing peptide receptors (GRPRs) overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer. The carboxylate groups of Lys¹Lys³(DOTA)-bombesin and folic acid were activated with HATU and also conjugated to the dendrimer. The conjugate was mixed with 1% HAuCl₄ followed by the addition of NaBH₄ and purified by ultrafiltration. Elemental analysis (EDS), particle size distribution (DLS), TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using ¹⁷⁷LuCl₃ or ⁶⁸GaCl₃ and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (>95%). Fluorescence results demonstrated that the presence of AuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15±2.72%). ¹⁷⁷Lu-dendrimer(AuNP)-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.

Fibroblast activation protein (FAP) is expressed in the microenvironment of most human epithelial tumors. ⁶⁸Ga-labeled FAP inhibitors based on the cyanopyrrolidine structure (FAPI) are currently used for the detection of the tumor microenvironment by PET imaging. This research aimed to design, synthesize and preclinically evaluate a new FAP inhibitor radiopharmaceutical based on the ^99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (^99mTc-iFAP) structure for SPECT imaging. Molecular docking for affinity calculations was performed using the AutoDock software. The chemical synthesis was based on a series of coupling reactions of 6-hidrazinylnicotinic acid (HYNIC) and D-alanine to a boronic acid derivative. The iFAP was prepared as a lyophilized formulation based on EDDA/SnCl₂ for labeling with ^99mTc. The radiochemical purity (R.P.) was verified via ITLC-SG and reversed-phase radio-HPLC. The stability in human serum was evaluated by size-exclusion HPLC. In vitro cell uptake was assessed using N30 stromal endometrial cells (FAP positive) and human fibroblasts (FAP negative). Biodistribution and tumor uptake were determined in Hep-G2 tumor-bearing nude mice, from which images were acquired using a micro-SPECT/CT. The iFAP ligand (Ki = 0.536 nm, AutoDock affinity), characterized by UV-Vis, FT-IR, ¹H–NMR and UPLC-mass spectroscopies, was synthesized with a chemical purity of 92%. The ^99mTc-iFAP was obtained with a R.P. >98%. In vitro and in vivo studies indicated high radiotracer stability in human serum (>95% at 24 h), specific recognition for FAP, high tumor uptake (7.05 ± 1.13% ID/g at 30 min) and fast kidney elimination. The results found in this research justify additional dosimetric and clinical studies to establish the sensitivity and specificity of the ^99mTc-iFAP.

Nanoparticles can be near infrared (NIR)-fluorescent (e.g., gold nanoparticles, quantum dots or carbon nanotubes) or can have magnetic properties (e.g., iron oxide nanoparticles). These optical or magnetic properties can be exploited for use in thermal therapy and molecular imaging. Radiolabeled nanoparticles have proven to be promising tools in the diagnosis and therapy of malignant processes due to their multivalency and as multi-modal imaging agents. Furthermore, these radiopharmaceuticals may function simultaneously as both radiotherapy systems and thermal-ablation systems. This review examines the application of radiolabeled nanoparticles in the development of multifunctional nanosystems for targeted therapy.