[68Ga]Ga-HBED-CC-DiAsp: A new renal function imaging agent

Abstract

Introduction: [⁶⁸Ga]Ga-EDTA ([⁶⁸Ga]Ga-ethylenediaminetetraacetic acid) was previously reported as a renal imaging agent for measuring GFR (glomerular filtration rate). In an effort to provide new agents with better in vivo characteristics for renal imaging, [⁶⁸Ga]Ga-HBED-CC-DiAsp (Di-Aspartic acid derivative of N,N'-bis [2-hydroxy-5-(carboxyethyl)benzyl]-ethylenediamine-N,N'-diacetic acid) was prepared and tested.

Method: HBED-CC-DiAsp was synthesized and labeled with [⁶⁸Ga]GaCl₄^- at room temperature. Plasma protein and red blood cells (RBC) binding were also evaluated. Biodistribution and dynamic PET imaging studies were performed in mice and rats, respectively.

Results: [⁶⁸Ga]Ga-HBED-CC-DiAsp was radiolabeled at room temperature by a one-step kit formulation in high purity without any purification (radiochemical purity >98%). Previous reports suggested that Ga-HBED-CC exhibited a higher stability constant and rapid chelating formation rate than that of Ga-EDTA (logK_GaL = 38.5 vs 22.1, respectively). In vitro stability studies indicated that it was stable up to 120 min. The log D_OW value, partition coefficient between n-octanol and water, was found to be -2.52 ± 0.08. Plasma protein and RBC binding was similar to that observed for [⁶⁸Ga]Ga-EDTA. Biodistribution and dynamic PET/CT imaging studies in rats revealed a rapid clearance primarily through the renal-urinary pathway. The PET-derived [⁶⁸Ga]Ga-HBED-CC-DiAsp renograms in rats showed an average time-to-peak of 3.6 ± 0.7 min which was similar to that observed for [⁶⁸Ga]Ga-EDTA (3.1 ± 0.5 min). The time-to-half-maximal activity was also comparable to that of [⁶⁸Ga]Ga-EDTA (8.8 vs 8.2 min, respectively). Pretreatment of probenecid, a renal tubular excretion inhibitor, showed no significant effect on renal excretion.

Conclusions: [⁶⁸Ga]Ga-HBED-CC-DiAsp could be prepared quickly at room temperature in high yield and purity. Results of in vitro studies and in vivo biodistribution in mice and rats suggested that [⁶⁸Ga]Ga-HBED-CC-DiAsp might be useful as a PET imaging agent for measurement of GFR.