First evaluation in humans of the new myocardial perfusion imaging agent 99mTcN-DBODC: safety, biodistribution and dosimetry assessment

Bis-(dimethoxypropylphosphinoethyl)ethoxyethylamine bis(N-ethoxyethyl)dithiocarbamato nitrido Tc-99m (99mTcN-DBODC) is a new monocationic compound that has been proposed for myocardial perfusion imaging. Previous studies in rats and dogs showed high safety margins and very promising biodistribution properties of this radiopharmaceutical in comparison to 99mTc-sestamibi and 99mTc-tetrofosmin. Aim of this preliminary phase I study is the evaluation of 99mTcN-DBODC safety profile, biodistribution and dosimetry in humans.Materials and Methods: Three healthy volunteers, mean age 40.7±12.0 (range 29-53), were evaluated after rest administration of the tracer under fasted conditions (mean dose 361.5±18.5 MBq). Biodistribution was studied by acquiring whole-body images up to 24 h postinjection. The MIRDOSE3 analysis program was used for radiation dosimetry calculations.Results: Safety parameters measured up to 24 h after injection revealed no clinically significant long-term drugrelated changes. Blood clearance of 99mTcN-DBODC was excellent (3.65%±1.33% after 10 min), and cumulative urinary clearance was 20.50%±10.52% of the injected activity within 24 h. Serial whole-body images showed that uptake in the heart (H), lung (L) and liver (Li) at 5 min after injection was 1.68%±0.30%, 1.51%±0.25%, and 10.77%±1.97% of administered dose, respectively. Radioactivity in Li decreased rapidly to reach 4.76%±1.93% at 60 min, and 2.90%±1.54% at 240 min. In contrast, a slow washout was observed in H (1.23%±0.16% at 240 min). Assuming a 4-h voiding period from the bladder, radiation dosimetry calculations indicate that the effective dose to the patient was 7.91 x 10-3 mSv/MBq.Conclusions: Preliminary phase I study data in humans showed that rest administration of 99mTcN-DBODC can yield high-quality myocardial images starting from 5 min postinjection. The estimated effective absorbed dose seems to be comparable with that of monocationic 99mTc-compounds currently employed in myocardial imaging. These data suggest that 99mTcN-DBODC is a promising new tracer with very favorable biodistribution characteristics for myocardial perfusion scintigraphy