Safety, biodistribution and radiation dosimetry of the Arg-Gly-Asp peptide 99mTc-maraciclatide in healthy volunteers

Abstract

Background 99mTc-Maraciclatide is a radiolabelled RGD (Arg-Gly-Asp) peptide that binds with high affinity to αvβ3 and αvβ5 integrins, common receptors upregulated in disease states involving angiogenesis and inflammation. As such, it holds promise as a novel diagnostic imaging agent for a range of pathological conditions. The present study provides the safety, biodistribution and radiation dosimetry of 99mTc-maraciclatide in healthy volunteers. Methods A phase 1, randomised, placebo-controlled study assessed the safety, biodistribution and radiation dosimetry of 99mTc-maraciclatide in healthy volunteers. Participants were randomised into three groups receiving 99mTc-maraciclatide and three chemical amounts of maraciclatide in an escalating dose protocol. Eight participants in each group received the required amount of maraciclatide via intravenous injection, with the remaining two receiving a placebo. Biodistribution was assessed by acquiring scintigraphic images at time points up to 24 h after a bolus injection of 99mTc-maraciclatide. 99mTc-maraciclatide activity in plasma and urine was measured up to 7 days post-administration. Results 99mTc-maraciclatide was safe and well tolerated, with no serious adverse events reported. Initial uptakes of 99mTc were highest in the gastrointestinal tract (20%), liver (15%), and lungs (9%). Similarly, the regions with the highest normalised cumulated activities were the contents of the urinary bladder and voided urine (3.4 ± 0.4 MBq*h/MBq), the combined walls of the small intestine and upper and lower large intestine (0.9 ± 0.2 MBq*h/MBq), liver (0.8 ± 0.2 MBq*h/MBq), lung (0.4 ± 0.1 MBq*h/MBq). The main route of 99mTc excretion was renal (55%), with a systemic urinary clearance of approximately 6.7 ml/min/kg. The pharmacokinetic analysis gave a mean apparent terminal elimination half-life of the unlabelled molecular maraciclatide of approximately 1 h, independent of dose. The mean ED per unit injected activity was 7.8 ± 0.8 µSv/MBq. Conclusion 99mTc-maraciclatide is a safe radiopharmaceutical formulation with a dosimetry profile similar to other 99mTc-based imaging agents.