Investigation of 177Lu-labeled HEDP, DPD, and IDP as potential bone pain palliation agents

Abstract

Application of bone-seeking radiopharmaceuticals is one of the modalities in the management of metastatic bone pain. The present study aimed to investigate the potential of 177 Lu-labeled phosphate/phosphonate ligands: 1-hydroxyethane 1,1-diphosphonic acid (HEDP), 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), and imidodiphosphate tetrasodium salt (IDP), as bone pain palliation agents. HEDP, DPD, and IDP were radiolabeled with 177 Lu in high radiolabeling yield (98.49%, 93.31%, and 90.69%, respectively), forming in vitro stable radiolabeled complexes in saline and human serum after 96 h. Biodistribution was followed by imaging studies and ex vivo measurement of radioactivity in organs in healthy Wistar rats. Significant bone accumulation and long retention even after 96 h (3.85 ± 0.91%ID/g), as well as relatively low uptake in soft tissue such as liver and spleen (<1%ID/g), were observed for 177 Lu-HEDP. Two other radiolabeled ligands showed lower accumulations in bone (<1% ID/g) and higher accumulations in liver and spleen at examined time points (>1.5% ID/g). Obtained results suggest that difference in the chemical structure of phosphonates/phosphates influences the rate of bone incorporation of 177 Lu-radiolabeled complexes. Desirable biodistribution pattern of 177 Lu-HEDP makes it suitable for its further preclinical investigations as a potential bone pain palliation agent.

Transmittance measurements in non-alternating magnetic field as reliable method for determining of heating properties of Fe3O4 magnetic nanoparticles

“…It is noteworthy that phosphates and phosphonates are water soluble and biocompatible and allow convenient stability and reduced cytotoxicity of MNPs for medical application [5]. Furthermore, they have a large binding a nity to the bone tissue which allows application in various medical conditions such as osteoporosis and bone tumors [6,7]. In addition, phosphates and phosphonates are higly e cient chelators.…”

“…Labeling of coated MNPs with 177 Lu 177 Lu-labeling of phosphates and phosphonates coated Fe 3 O 4 MNPs was obtained using the method previously described [11,16]. Brie y, 177 LuCl 3 solution (approximately 185 MBq in 5 µl) was added to an aqueous suspension of coated Fe 3 O 4 MNPs (5 mg/ml at pH 4.5) and incubated at room temperature with continual stirring for 1 h. To quantify the radiolabeling yield of 177 Lu-labeled MNPs and their radiochemical purity after puri cation by magnetic decantation, ITLC was performed on SG sheets with 0.1 M acetate buffer as the mobile phase.…”