Development of labelled platelets as radiopharmaceuticals

Abstract

The choice of platelet radiolabelling agent and labelling techniquehas been evaluated since accurate diagnosis is dependent on retaining normal function of the labelled cells. The two labelling agents,indium-111 oxine and indium-111 tropolone were used and indium-111 oxine was found to be the superior platelet labelling agent. Maintenance of viability was demonstrated using in vitro aggregation tests. Having established a successful labelling method, techniques to determine in vivo platelet kinetics were evaluated and protocols for splenic uptake and platelet survival were developed. Hepatic uptake was investigated in order to assess in vivo platelet function of the manipulated sample since liver time-activity curves are sensitive indicators of platelet activation. A protocol was developed to compare the blood and liver activity curves. Compartmental analysis techniques for determining splenic blood flow and intrasplenic platelet transittime were also used but found to be difficult to adopt as the calculation is dependent upon a subjective estimate. Further work is required to establish a satisfactory protocol. Radioactively labelled platelets have successfully been used in the diagnosis of idiopathic thrombocytopenia (5 patients) and deep vein thrombosis (7 patients). The results have been clinically useful in the further management of the patient. Platelet kinetics were also investigated in patients with inflammatory bowel disease (12 patients). In vitro aggregation tests on such patients had demonstrated abnormal platelet function. It was thought that this abnormality may contribute to the increase in thrombotic complications reported in inflammatory bowel disease.Therefore, kinetics studies were performed to determine whether abnormalities in distribution and survival could be detected. However, platelet distribution and survival were found to be within the normal ranges.