Over the past several decades nuclear medicine turned into an integral part of clinical practice in developed countries. The therapeutic radiopharmaceuticals (RPh), developed and currently used in Russia, are applied for treatment of oncological diseases, but due to their versatility, RPh can be useful in other fields of medicine.
For this purpose formulation development of a medication on the basis of β--emitting radionuclide 188Re as an active substance and human serum albumin microspheres (HSA) as a carrier was carried out.
The benefits of 188Re include the possibility to obtain it in medical institutions in the form of perrhenate ions (ReO4)– by means of the 188W/188Re generator, or in specialized institutions using the extraction technique. In both cases, the obtained substance allows to prepare RPh without a carrier, which is an undeniable advantage and leads to an increase of the medication specific potency.
HSA were chosen due to their biodegradability, affinity to the human body, high stability in vivo and in vitro, and also tight binding of 188Re to a sulfur atom of cysteine in the polypeptide. Various sizes of microspheres in RPh make it possible to create medications with different pharmacodynamic and pharmacokinetic attributes.
We investigated the influence of auxiliary substances on the labelling degree. Since 188Re (VII) is incapable to form bonds with HSA, a reducing agent was additionally used to facilitate 188Re (IV) production. An antioxidant in RPh contributes to reducing the possible negative effects of radiolysis. A transchelator promotes the better incorporation of 188Re into the polypeptide molecule composition by forming a complex in a low stability constant, followed by a re-ligand effect on the polypeptide molecule. An emulsifier improves HSA hydrophilic properties.
In view of the foregoing, we carried out works to study the effect and search for optimum concentration values of auxiliary substances necessary to achieve a labelling yield of at least 95%.
The quality analysis of the finished RPh was carried out taking into account two parameters: pH and the value of radiochemical impurities (the ratio of activity of 188Re ions unbound to HSA to the total activity of the medication). The timing stability of the prepared RPh was also studied; the study was conducted within 72 hours from the time of preparation in physiological solution. It was found out that during this period of time 188Re is tightly bound to HSA and is not released into the external environment.
Thus, this pharmaceutical composition is an excellent preformulation for topical treatment of joint diseases by means of intra-articular administration of the medication.