Clinical Utility : Protocol Optimization

A Phase II, open-label, multi-center trial involving four sites in Europe compared 1- and 2-day MYOVIEW protocols and also compared MYOVIEW-derived diagnoses to those derived from a stress/redistribution TI-201 imaging protocol in 55 evaluable patients with ischemic heart disease.⁷ The basic study design is shown in Figure 5. Patients initially underwent thallium imaging and received 55.5 to 75MBq (1.5 to 2mCi) of TI-201. After 3 to 7 days, 296 to 370MBq (8 to 10mCi) of Tc-99m-tetrofosmin was administered at rest. On a separate day, patients received 296 to 370MBq (8 to 10mCi) of Tc-99m-tetrofosmin at peak exercise and 888 to 1110MBq (24 to 30mCi) at rest, approximately 4 hours later. Imaging was performed by obtaining planar static images in four standard views (anterior, 40° left anterior oblique (LAO), 70° LAO, and left lateral) at 10 minutes and 4 hours post- TI-201 injection or 5, 30, 60, 90, 120, and 240 minutes post-MYOVIEW injection. Scan segments were diagnosed as either normal, ischemic, infarct, mixed, or equivocal.⁷

Results indicated that both 1- and 2-day MYOVIEW protocols provided high- quality,. diagnostically useful images of the heart that were of similar quality as those derived from the thallium procedure. The unblinded interpretation of scans produced by TI-201 and MYOVIEW imaging resulted in the same diagnosis in approximately 80% of the cases.⁷

Figure 5. - Phase II basic trial design.⁷

An extension of this Phase II trial examined the clinical utility of lower MYOVIEW doses.⁷ Six patients received doses of 185 to 296MBq (5 to 8mCi) at peak exercise and 555 to 888MBq (15 to 24mCi) at rest 4 hours later in a 1-day protocol. Images obtained within 1 hour of injection were found to be of a high diagnostic quality.⁷

The Phase II trial also assessed the biokinetics of MYOVIEW. After visual analysis of the images, the defect-to-normal myocardial wall ratios were calculated from stress and same-day rest reinjection images. Figure 6 shows that in 13 patients with reversible defects (identified by both MYOVIEW and TI-201) and in another 13 patients with fixed defects there was no significant redistribution. Furthermore, slow myocardial washout of Tc-99m-tetrofosmin (4% to 5% per hour after exercise and 0.4% to 0.6% per hour after rest) allowed accurate stress and rest imaging for up to 4 hours post-injection.⁵

Figure 6. - Defect-to-normal myocardial ratio of Tc-99m-tetrofosmin with fixed and reversible defects; note absence of redistribution.⁵

The biokinetics of MYOVIEW was further assessed in 20 patients with suspected CAD.¹⁴ A 1-day protocol was employed during which patients received 222 to 296MBq (6 to 8mCi) Tc-99m-tetrofosmin at peak exercise followed 4 hours later by a resting dose of 814 to 888MBq (22 to 24mCi). Serial planar images obtained in the left oblique view were acquired for 5 minutes at intervals between 5 and 180 minutes post-injection.¹⁴
Good to excellent quality images were obtained for all patients in the study.¹⁴ Myocardial delineation was judged to be excellent with minimal background and little interpretive interference due to subdiaphragmatic or gallbladder uptake (Figure 7).

Figure 7. - Serial images following exercise and rest injections of MYOVIEW in a patient with partially reversible septal and apical perfusion abnormality. Note the low subdiaphragmatic activity as early as 5 min after the exercise injection.¹⁴

Distribution data obtained during stress imaging revealed that the heart had the highest Tc-99m-tetrofosmin activity from 15 to 180 minutes post-injection. In addition, heart- to-organ ratios during stress were greater than 1.0 at all times during the study period. In contrast, rest images showed that the liver, gastrointestinal (GI) tract, and gallbladder had higher activity than the heart for the first 15 to 30 minutes, but the heart had higher activities thereafter due to rapid tracer clearance from the former organs. Heart-to-organ ratios during rest were less than 1.0 during the first 15 minutes for liver and GI tract, but were greater than 1.0 for all organs at 30 minutes post-administration of Tc-99m-tetrofosmin.¹⁴

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