Biodistribution and Radiation Dosimetry of the Integrin Marker 64Cu-BaBaSar-RGD2 Determined from Whole-Body PET/CT in a Non-human Primate

Introduction: Cu-64 BaBaSar RGD(2) is a positron emission radiotracer taken up by integrin alpha(v)beta(3), which is overexpressed in many malignancies. The aim of this study was to evaluate the biodistribution of Cu-64-BaBaSar-RGD(2) in a non-human primate with positron emission tomography (PET) and to estimate the absorbed doses in major organs for human. Materials and Methods: Whole-body PET imaging was done on a Siemens Biograph scanner with a male macaque monkey. After an i.v. injection of 13.1-19.7 MBq/kg of Cu-64-BaBaSar-RGD(2), whole body scan was collected for a total duration of 180 min. Attenuation and scatter corrections were applied to reconstructions of the whole-body emission scan. After image reconstruction, three-dimensional volumes of interest (V01) were hand -drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time -activity curves (TACs) for each VOI were obtained, and residence times of each organ were calculated by integration of the time -activity curves. Human absorbed doses were estimated using the standard human model in OLIN DA/EXM software. Results: Injection of Cu-64-BaBaSar-RGD(2) was well-tolerated in the macaque monkey, with no serious tracer -related adverse events observed. Cu-64-BaBaSar-RGD(2) was cleared rapidly from the blood pool, with a 12.1 -min biological half-life. Increased Cu-64-BaBaSar-RGD(2) uptake was observed in the kidneys, and bladder, with mean percentage injected dose (ID%) values at 1 h after injection similar to 35.50 +/- 6.47 and 36.89 +/- 5.48, respectively. The calculated effective dose was 15.30 +/- 2.211 mu Sv/MBq, and the kidneys had the highest absorbed dose at 108.43 +/- 16.41 mu Gy/MBq using the non-voiding model. For an injected activity of 925 MBq Cu-64 for human, the effective dose would be 14.2 +/- 2.1 mSv. Discussion: Due to the limited availability of the primates, we evaluated Cu-64-BaBaSar-RGD(2) in the same monkey using three imaging sessions. Measured absorbed doses and effective doses of Cu-64-BaBaSar-RGD(2) are comparable to other reported RGDderived radiopharmaceuticals labeled with Cu-64 and F-18 Therefore, Cu-64-BaBaSar-RGD(2) can be safely injected into humans for studying integrin alpha(v)beta(3) expression non-invasively.