Radiolabeling, quality control, biodistribution, and imaging studies of ¹⁷⁷Lu‐ibandronate

Abstract

The purposes of this study were as follows: (1) to radiolabel ibandronic acid (IBA, a third‐generation bisphosphonate) with 177Lu, investigating optimal labeling conditions, and (2) to analyze biodistribution and imaging properties of intravenous 177Lu‐ibandronate (177Lu‐IBA) administered in animals. 177Lu‐labeled methylene diphosphonate (177Lu‐MDP) served as a comparator agent. Differing proportions of IBA solution and 177LuCl3 solution were combined to determine an optimal ratio for radiolabeling purposes, varying pH, temperature, and time to establish ideal reactivity conditions. Radiochemical purity of the labeled compounds was then assessed by paper chromatography. In vitro and in vivo stabilities were also measured at specific time intervals. In Kunming mice, biodistributions of 177Lu‐IBA and 177Lu‐MDP and respective agent activities in various organs were monitored by gamma counter, and we performed single photon computed tomography/computed tomography (SPECT/CT) imaging of 177Lu‐IBA in normal New Zealand White rabbits. Radiolabeling yields for 177Lu‐IBA proved to be >97% within 30 minutes at 90°C, and its radiochemical purity ensured stability in vitro and in vivo. Furthermore, we found that 177Lu‐IBA is readily soluble in water, showing higher skeletal uptake than 177Lu‐MDP but lower uptake by liver and spleen. The image quality of 177Lu‐IBA was so clear that even after 6 days, analysis was still feasible.

Preparation, Characterization, and Preliminary Imaging Study of [188Re]Re‐Ibandronate as a Novel Theranostic Radiopharmaceutical for Bone Metastasis

“…It has the advantages of simultaneous treatment of multiple metastases, repeatability, and combination with other treatments [2]. Moreover, it can reduce or delay the incidence of skeletal-related events [3] [4,5]. However, every radiopharmaceutical has its advantages and disadvantages.…”

A study on the preparation, evaluation of biological characteristics, and preliminary imaging of [188Re]Re-ibandronate

“…Numerous radiopharmaceuticals have been used to target and relieve bone pain since the introduction of radionuclides to treat bone pain in the 1940s [19]. [6,9]. However, each radiopharmaceutical has its own advantages and disadvantages.…”

“…The currently available treatments for bone metastasis are chemotherapy, radiotherapy, bisphosphonate therapy, hormone therapy, and the use of painkillers [5]. However, the aforementioned methods have some limitations [6]. The use of bone-seeking radiopharmaceuticals is another effective method to relieve bone pain.…”

“…Moreover, it can reduce or postpone the incidence of skeletal-related events [8]. There are several radionuclides available for bone-targeted radionuclide therapy, including 89 Sr, 153 Sm, 186 Re, 188 Re, 177 Lu, and 223 Ra [6,9]. 89 Sr and 223 Ra are calcium mimetic radionuclides.…”

Human Absorbed Dose Evaluation of [177Lu]Lu-IBA as a Bone Palliative Candidate

“…Lutetium-177 has a maximum beta energy of 0.5 MeV and a maximum tissue range of~2 mm. It also emits γ-radiations of 113 keV (6.4 %) and 208 keV (11 %), which enables γ-scintigraphy to facilitate dosimetry and disease staging [7,8]. These properties makes it an appropriate choice to produce different radiopharmaceuticals based on uses.…”