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.

^99mTc-HYNIC-DA incorporated into HDL nanoparticles can be used to image SR-B1 positive tumors.

Background Clinical studies in women using technetium-99m (^99mTc)-Bombesin have shown successful radionuclide imaging of breast tumours overexpressing gastrin-releasing peptide receptors (GRPRs). Recent studies have demonstrated that most breast tumours overexpress folate receptors (FRα). Aim The aim of this work was to synthesize the Lys¹(α,γ-Folate)-Lys³(^99mTc-EDDA/HYNIC)-Bombesin (1–14) conjugate (^99mTc-Bombesin–Folate), as well as to assess the in-vitro and in-vivo potential of the radiopharmaceutical to target FRα and GRPR. Methods Lys¹Lys³(HYNIC)-Bombesin (1–14) was conjugated to folic acid and the product was purified by size-exclusion high-performance liquid chromatography. Ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were used for chemical characterization. ^99mTc labelling was performed using ethylenediamine-N,N′-diacetic acid/tricine as coligands. In-vitro binding studies were carried out in T47D breast cancer cells (positive for FRα and GRPR). Biodistribution studies and micro-single-photon emission computed tomography/computed tomography imaging were carried out on athymic mice with T47D-induced tumours. Results High-performance liquid chromatography analyses indicated that the radioconjugate was obtained with high radiochemical purity (96±2.1%). In-vitro and in-vivo results showed significant uptake of the radiopharmaceutical in T47D cells and tumours (5.43% ID/g), which was significantly inhibited by preincubation with cold folic acid or cold Bombesin. Conclusion The ^99mTc-Bombesin–folate heterobivalent radiopharmaceutical significantly enhances in-vivo tumour uptake because of the concomitant interaction with FRα and GRPR.