Clinical study with a new radiopharmaceutical (RP-517) for the in vivo labeling of neutrophils with 99mTc

RP-517 is a 99mTc labeled antagonist to the LTB4 receptor which, with a single i.v. injection, allows the in vivo labeling of neutrophils for the detection and localization of infectious and/or inflammatory foci. Aim: To determine: 1) the safety and tolerance of the radiopharmaceutical in humans; 2) its pharmacokinetics and dosimetry; 3) its preliminary efficacy for the detection and localization of infectious foci. Materials and Methods: 20 subjects (14M, 6F) received 592 ± 111 MBq (16 ± 3 mCi) of RP-517 intravenously. All subjects were evaluated (medical history, physical exam, vital signs, ECG, blood and urine analysis) before and at several times up to 24 hours post-injection of RP-517. Blood samples were taken to determine pharmacokinetics and blood clearance. Urine and feces were collected to measure excretion. For dosimetry determination, whole body images, one transmission pre-injection and sequential emission images post-injection, were obtained with a dual head gamma camera (ADAC) in 2 patients and 14 volunteers. Sequential focal images were obtained in 4 patients. The presence of infection was determined by culture and/or follow-up. Results: There were no adverse clinical events or clinically significant changes in any of the laboratory analysis parameters, ECG or vital signs. RP-517 clears the blood mainly through the hepatobiliary system. The critical organ is the gall bladder wall, followed by the intestinal wall. A suggested maximum injected dose of about 740MBq of RP-517 would deliver ≤ 50 mGy to the critical organ. There were 6 patients with suspicion of infection: in 2 of them the infection was proven; a third subject had 2 suspected infectious foci, one was proven, the other one was equivocal; at the time of imaging, there was no infections process in the other 3 subjects. RP-517 images showed a clear and persistent uptake in the 3 proven infectious foci, was negative in the equivocal one and in the three patients without infection. Conclusion: RP-517 is safe and well tolerated. Dosimetry calculations suggest about 740MBq as the maximum injected dose. The promising preliminary efficacy justify additional clinical studies to determine RP-517's true diagnostic value