Phase 1 clinical trial results for high specific activity Ultratrace Iobenguane I 123

Objectives Very high specific activity Iobenguane I 123 (Ultratrace) is manufactured with a novel solid state precursor to produce final drug in high yield and purity under mild reaction conditions. This Phase 1 study reports Ultratrace tissue distribution, organ dosimetry, and safety.

Methods Ultratrace was delivered sterile and ready to use at the clinical site. Radiochemical purity and pharmaceutical attributes included: visual appearance, identity and purity using HPLC, osmolality, endotoxins, sterility, pH, and chemical purity and content with LC/MS. Twelve healthy subjects (6M, 6F) received 370 MBq, ant/post whole body images acquired through 48h, and heart/mediastinal ratios (H/M) measured.

Results Content of all iobenguane related species for the Ultratrace formulation was 2.56 ± 0.43 µmol/mL. Radioactive concentration at TOC was 166 - 203 MBq/mL (4.5-5.5 mCi/mL) for an “effective” specific activity 1,900 - 2,100 Ci/mol. Ultratrace iobenguane specific activity was ~85x higher than commercial iobenguane I-123 AdreView. No test article related adverse events were observed. Whole body imaging showed rapid and consistent heart uptake, rapid blood clearance, and predominantly renal excretion. The 1 and 4 hour H/M were 2.047 + 0.223 and 2.203 + 0.285 (mean+STD). The OLINDA/EXM estimates (mSy/Bq) of greatest target organs were: urinary bladder wall (0.073), intestinal walls (0.031-0.071), salivary glands (0.064), thyroid (0.055) and kidneys (0.028). Effective dose was 0.027 mSv/MBq.

Conclusions Ultratrace Iobenguane I 123 solution for injection demonstrates a significant increase in effective specific activity. This formulation produces high purity, and constant final drug product solution. It is safe, and yields vivid human Imaging in normal adults with acceptable radiation dosimetry.

Research Support NIH SBIR R44 CA 13039