The objective of this work is to evaluate the potential effect of cardiac stress exercise on the\naccumulation of [123I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise\nnormal myocardium in healthy volunteers, and to determine the impact of exercise on [123I]IAZA\npharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies\nof focal myocardial hypoxia in cardiac patients using [123I]IAZA. Three healthy male volunteers\nran the ââ?¬Ë?Bruceââ?¬â?¢ treadmill protocol, a clinically-accepted protocol designed to expose myocardial\nischemia in patients. The ââ?¬Ë?Bruceââ?¬â?¢ criterion heart rate is 85% of [220ââ?¬â??age]. Approximately one minute\nbefore reaching this level, [123I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1ââ?¬â??3 min) single\nintravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for\nan additional 1 min before being transferred to a gamma camera. Serum samples were collected\nfrom the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h\npost injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for\n[123I]IAZA and total radioactivity (total[123I]) using compartmental and noncompartmental analyses.\nWhole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and\nscintigraphic images were compared to previously published [123I]IAZA data from healthy volunteers\nrest. Following exercise stress, both [123I]IAZA and total[123I] exhibited bi-exponential decline profiles,\nwith rapid distribution phases [half-lives (t1/2Ã?±) of 1.2 and 1.4 min, respectively], followed by slower\nelimination phases [t1/2Ã?² of 195 and 290 min, respectively]. Total body clearance (CLTB) and the steady\nstate volume of distribution (Vss) were 0.647 L/kg and 185 mL/min, respectively, for [123I]IAZA\nand 0.785 L/kg and 135 mL/min, respectively, for total[123I]. The t1/2Ã?², CLTB and Vss values were\ncomparable to those reported previously for rested volunteers. The t1/2Ã?± was approximately 4-fold\nshorter for [123I]IAZA and approximately 3-fold shorter for total[123I] under exercise relative to rested\nsubjects. The heart region was visualized in early whole body scintigraphic images, but later images\nshowed no accumulated radioactivity in this region, and no differences from images reported for\nrested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle\nwas consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [123I]IAZA in\nexercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers.\nThere was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium,\nsupporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable\nmyocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t1/2Ã?± was\nshortened, reflecting increased cardiac output associated with exercise. It is concluded that because\n[123I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency.\n[123I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients\nundergoing stress-test-based diagnosis.
Loading....