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Evaluation of ^99mTc-RP128 as a Potential Inflammation Imaging Agent: Human Dosimetry and First Clinical Results

Division of Nuclear Medicine, Free University Hospital Brussels, Brussels, Belgium; and Resolution Pharmaceuticals Inc., Mississauga, Ontario, Canada

^99mTc-RP128 is a bifunctional peptide chelate designed to target the tuftsin receptor, expressed by neutrophils, monocytes, and macrophages. Studies in animal models of both infectious and noninfectious inflammation have shown a positive correlation between accumulation of ^99mTc-RP128 and quantitative measures of inflammation. A phase 1 trial was conducted with the objective of determining the safety, biodistribution, and human dosimetry of ^99mTc-RP128 in eight healthy volunteers. For evaluation of the potential of ^99mTc-RP128 for imaging sites of inflammation, 10 patients with active rheumatoid arthritis were studied. Methods: Normal biodistribution was determined using the conjugate view method up to 24 h after intravenous injection of 280 MBq ^99mTc-RP128. Dosimetry calculations were based on standard MIRD methodology, using the International Commission on Radiological Protection model 30 of the gastrointestinal tract and a voiding bladder model with an interval of 4.8 h. For rheumatoid arthritis patients, whole-body scans and spot views of the hands, knees, and feet were obtained at 1 and 3 h after injection of 475 MBq ^99mTc-RP128. Results: ^99mTc-RP128 was cleared rapidly from the blood by renal excretion, and no major organs showed significant accumulation. The synovia of the major joints were visualized for all subjects. The effective dose equivalent and the effective dose were calculated to be 0.011 and 0.0094 mSv/MBq, respectively. The highest dose was to the bladder wall, which received 0.076 mGy/MBq. In all rheumatoid arthritis patients, we observed a markedly increased uptake in several affected joints. Painful and swollen joints were detected with a sensitivity of 76% and 69%, respectively. Seventy-three percent of the joints with radiographic signs of erosion were scintigraphically positive. In some patients, lines of increased activity were observed and were considered to correspond to uptake in the synovium lining tendon sheaths in the wrists and hands. Conclusion: This study shows that ^99mTc-RP128 is safe and can successfully be used to visualize clinically affected joints in patients with long-standing rheumatoid arthritis. A proposed radioactive dose of 450–500 MBq will produce an effective dose well within the range of effective doses for commonly used radiopharmaceuticals.

Key Words: ^99mTc-RP128 • peptides • inflammation • tuftsin

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