Different Models for Cost-Effective Fractionation of Bone Radiopharmaceuticals; Methylene Diphosphonate (MDP) & Hydroxymethylene Diphosphonate (HDP)

Abstract

Introduction:
The aim of this work is to study the availability of MDP & HDP cold kit fractionation with different modalities of different storage conditions and temperatures as a function of time elapsed after fractionation.
Materials and Methods:
Samples were taken by adding a definite amount of 0.9 NaCl solution to the cold kit and the modes of fractionation used were:
1) Non-Oxidation condition, freezing (-20 to -28 oC) fractionation,
2) Non-Oxidation Condition, refrigerated (0 to 4oC) fractionation
3) Oxidation Condition, freezing fractionation.
These modes of fractionation were studied for a period of 3 months depending upon the need of fractionation time for each radiopharmaceutical and on the changes in the results obtained for the different fractionation procedure. Instant Thin Layer Chromatography (ITLC-SG) with Acetone & 0.9 NaCl as solvents was simply used to determine the percentage Radiochemical Purity (%RCP) of the target ligand (99mTc-MDP & 99mTc-HDP) which was considered acceptable if greater than 95%. The concentration of the 2 main impurities TcO4 & TcO2 should not exceed 5%.
Results & Discussion:
MDP: The first mode of fractionation, all the samples studied with a mean %RCP of 98.37%, 98.56% and 98.69% for the first, second and third months respectively showed an excellent fractionation procedure under this condition. Refrigerator and syringe sampling modes of fractionation procedures were ultimately successful for three months under these conditions with a %RCP of 98.74% and 98.84% respectively.
HDP: Efficient fractionation procedure was verified in the first mode of fractionation with a %RCP of 98.28%, 98.08% and 98.07% for the first, second and third months of fractionation. In refrigerator fractionation mode, a mean %RCP of the HDP complex of 97.15% was obtained for 3 months study, showing a successful fractionation procedure for this long time period. Fractionation procedure for the syringe-stored samples showed fluctuating results with acceptable %RCP in the first and third months of 98.38% and 96.63% respectively and failed %RCP in the second month 88.88% respectively. Stannous augmentation was a good solution to overcome this problem as the degraded radiochemical purity was always accompanied with increase in the 99mTc-pertechnetate concentration.
Conclusion:
MDP and HDP cold kits reflected an excellent behavior when fractionated for a period from 3 months with all studies fractionation modules except the fluctuated results of HDP with the oxidation condition fractionation, which can be recovered by augmentation of stannous ions. The practicality of the second fractionation mode should be studied from the sterility point of view.