Development of a Potential Bone-Seeking Radiopharmaceutical by Sodium Pyrophosphate Labeled ¹⁸⁸Rhenium (¹⁸⁸Re-PYP) for Bone Pain Palliation

Abstract

Background: Technetium-99m (99mTc)-pyrophosphate (PYP) has been widely utilized in diagnosing bone disorders and certain cardiac conditions, such as amyloidosis, allowing for accurate imaging and detection of abnormalities within heart tissue. Rhenium, being in the same group as technetium in the periodic table, shares similar chemical properties. Rhenium-188 (188Re) possesses favorable nuclear properties for theranostic applications. Objectives: This study focused on labeling sodium PYP with 188Re and its biodistribution. Methods: Different samples with varying amounts of PYP (5 - 22 mg), SnCl2.2H2O (0.2 - 6.0 mg), and ascorbic acid (0.3 - 7 mg) were prepared in vials. Initially, 0.08 mg of potassium perrhenate as a carrier in 1 mL saline was added to each vial. Subsequently, 370 - 3700 MBq of 188ReO4− was added to the initial solution. The pH of the solutions was varied between 3 and 8. The compound was shaken vigorously for 30 seconds. Product incubation was performed in a secured container for 30 minutes at room temperature. Results: Maximum labeling yield was achieved with 10 mg of PYP, 1 mg of SnCl2.2H2O, 0.3 mg of ascorbic acid, and 0.08 mg of potassium perrhenate as a carrier in 1 mL with 370 MBq of 188ReO4− at pH 5. This compound showed good stability, and a radiochemical purity of 98.96% ± 0.1% was obtained. The biodistribution results of the radiolabeled ligand revealed that the maximum affinity for 188Re-PYP was for bone after 4 hours, which was 2.24% ± 0.667% ID/g. The maximum uptake for the kidney, spleen, and liver was 1.53% ± 0.378%, 0.13% ± 0.086%, and 0.18% ± 0.12% ID/g, respectively. Conclusions: The present study investigated the initial labeling efficiency of 188Re-PYP along with its biodistribution and in vitro stability. The 188Re-PYP conjugate, prepared under optimized conditions, demonstrated radiochemical purity and stability. The biodistribution of the compound in mice exhibited high affinity for bone, whereas the complex was eliminated through the kidneys.