New 68Ga-labeled skeletal-imaging agents for positron scintigraphy.

The present skeletal-imaging agents labeled with radiogallium rely upon carrier gallium to augment bone uptake; no gallium-labeled bone-imaging agent free of this disadvantage is available. In attempts to develop such agents, we prepared 68Ga-ethylenediaminetetramethylene phosphonate (68Gs-EDTMP) and 68Ga-diethylenetriaminepentamethylene phosphonate (68Ga-DTPMP) and determined their biologic distributions in rats and dogs. These compounds combine the bone-seeking characteristics of phosphonic acid and the complexing ability of EDTA and DTPA analogs. The chelates are administered without gallium carrier. In rats, 50-60% of the carrier-free dose accumulates in bone at 1 hr after intravenous injection, while 25--30% is excreted through the urine. In dogs, at 3 hr after intravenous injection 35% is found in bone. Although the general patterns of organ distribution of the two 68Ga chelates are similar, 68Ga-EDTMP appears superior because of its faster blood clearance. Bone images obtained with this compound in dogs, using a multidetector positron camera, are presented. The optimum time for imaging was found to be 2.5--3 hr after injection.