The physical characteristics of the Sn and S colloids obtained were analyzed to select the formulation, which showed the best parameters.
It has been well established by other investigators that the radiopharmaceutical particle size must be small enough to be phagocyted by the superficial cells of the synovium but not so small as to facilitate a fast biological clearance from the articulation [12
] was taken into account.
Different optimal ranges of particle sizes considered as ideal for radiosynovectomy have been reported [4
]. Differences found in the literature are probably based on the use of different methodologies to measure particle size. Other parameters were considered in our study, such as total particle volume or the sum of different volume sizes grouped in the ranges of interest. In the same way, another criteria were colloid surface area in selected ranges.
As radioactivity was deposited as a function of volume or surface of the particles, methodologies that put this into evidence and analyzed further modifications of the formulation in the same way should enable to arrive to consistent conclusions. It was found that in the 2–10 microns range, the Sn colloid attained a greater number, volume and surface are of particles than those of the S colloid.
Nearly 95% of the S colloid volume belonged to those particles larger than 100 microns, in spite of the fact that these were a very small percentage of the whole preparation. On the other hand, 60% of the Sn colloid volume was composed of particles with size in the selected range, while only 5% of the volume of the S autoclaved colloid gave particles sizes in the same range.
Three-dimensional plot representation turned out to be an interesting tool to study valuable information about the behavior of colloids to study particle volume or surface area as a function of number, in a particular range.
The correlation of the two colloid characterization methodologies suggested that when a kit was evaluated by membrane filtration erroneous results might have been obtained, such as overestimation of particle percentage due to non-specific retention on the filter. This phenomenon was observed for those particles larger than 5 microns, immediately after kit preparation, where the electrical properties of the colloid were more significant. Besides that, only laser diffraction methodology provided a method to evaluate differences due to the aging of kit formulation during the first week after kit preparation and during the first 24 hours after similar conditions to those of labeling of tin colloid. This last observation made it possible to define a shelf life of 24 hours for the labeled colloid.
The effect of tensoactive addition was also studied (Tween 80®
) in order to facilitate radiopharmaceutical administration. It was thought that this addition would not diminish colloid stability due to counteract particle coalition. It is known that small particles will show a gradual increase in size, a phenomenon that is called Ostwald maturation [16
]. Smaller particles have a greater solubility than larger ones of the same preparation, due to their higher surface area and free superficial energy. Spontaneous enlargement of colloidal dispersions due to aging, is accelerated by an increase in precipitate solubility and may be delayed by diminishing their solubility or by adding very small amounts of tensoactive agents that are absorbed on the surface of the particle. Taking this into account, Tween 80 was added to the formulation, but results were different to those described above because particle volume showed an increase after kit preparation.
The radiochemical purity of the 188Re-Sn colloid showed an increase after heating the colloid from thirty to sixty minutes. This fact implied a slow reaction, which required this time to reach the best value (95%). Activity distribution in the different ranges of particle size was not affected by heating time. Activity absorption on each particle is an unspecific process. Eighty percent of the activity was kept in those particles retained by the 5 microns filter – for heating time of 30, 60 or 90 min-, and these particles were a small amount of the total preparation. Ninety eight percent of particles, in number, had sizes below 3 microns and concentrated only about 10% of the whole activity. This fact confirmed to us that particle volume or surface area were the main parameters to be taken into account. Therefore particle size distribution did not correlate with activity data distribution.
More important changes in particle distribution were detected during the first week after kit preparation, this being the time needed for colloid stabilization. No further relevant changes were noted during the stability study so that eight weeks of shelf life could be safely proposed.
In vivo studies have shown that 48 hours post-administration knee retention was higher than 90%. One and three percent of activity was detected in the kidney and liver respectively, which can be attributed to the smallest particles (less than 1 micron); activities of urine samples were at background levels.