Synthesis and in vivo evaluation of gallium-68-labeled glycine and hippurate conjugates for positron emission tomography renography.

The objective of this study was to evaluate four new (68) Ga-labeled 1,4,7,10-cyclododeca-1,4,7,10-tetraacetic acid (DOTA)/1,4,7-triazacyclononane-1,4,7-triacetic acid derived (NODAGA)-glycine/hippurate conjugates and select a lead candidate for potential application in positron emission tomography (PET) renography. The non-metallated conjugates were synthesized by a solid phase peptide synthesis method. The (68) Ga labeling was achieved by reacting an excess of the non-metallated conjugate with (68) GaCl4 (-) at pH -4.5 and 10-min incubation either at room temperature for NODAGA or 90 °C for DOTA. Radiochemical purity of all (68) Ga conjugates was found to be >98%. (68) Ga-NODAGA-glycine displayed the lowest serum protein binding (0.4%) in vitro among the four (68) Ga conjugates. Biodistribution of (68) Ga conjugates in healthy Sprague Dawley rats at 1-h post-injection revealed an efficient clearance from circulation primarily through the renal-urinary pathway with <0.2% of injected dose per gram remaining in the blood. The kidney/blood and kidney/muscle ratios of (68) Ga-NODAGA-glycine were significantly higher than other (68) Ga conjugates. On the basis of these results, (68) Ga-NODAGA-glycine was selected as the lead candidate. (68) Ga-NODAGA-glycine PET renograms obtained in healthy rats suggest (68) Ga-NODAGA-glycine as a PET alternate of (99m) Tc-Diethylenetriaminepentaacetic acid (DTPA).

Establishing a threshold for 131I bioassay in nuclear medicine personnel.

Since the late 1970's, manufacturers in nuclear medicine have reformulated the I solution to reduce the volatility of the iodine. There has also been an increase in use of the iodide in encapsulated form. Per the requirement of the current U.S. Nuclear Regulatory Commission (U.S. NRC) regulation, with the available results on the volatility of the reformulated radioiodine, we review the I bioassay program for nuclear medicine workers. Our analysis shows the threshold quantity for bioassay monitoring for the routine use of I in nuclear medicine is much higher than the criteria set in U.S. NRC Regulatory Guide 8.20. The latter is a broad bioassay guideline for the general usage of radioactive iodine. For treatment of thyroid carcinoma and hyperthyroidism, a single therapeutic I dose large enough to yield a detectable thyroid burden is very unlikely to occur in a nuclear medicine clinic. Accidental ingestion or inhalation would be an exception to our conclusion. Based on this analysis, we propose a new bioassay policy for the routine use of I in nuclear medicine clinics.