Minimizing liver uptake of cationic 99mTc radiotracers with ether and crown ether functional groups

Figure 1 ^99mTc radiotracers useful for heart imaging. ^99mTc-Sestamibi, ^99mTc-Tetrofosmin and ^99mTc-Teboroxime have been approved as commercial radiopharmaceuticals for myocardial perfusion imaging.

Figure 2 Cationic ^99mTc-nitrido complexes with fast liver clearance and excellent heart/liver ratios. Both ^99mTcN-DBODC5 and ^99mTcN-MPO are under clinical investigation as new myocardial perfusion imaging agents.

Figure 3 Crown ether-containing DTCs, bisphosphines and their cationic ^99mTc-nitrido complexes.

Figure 4 Cationic ^99mTc(I)-tricarbonyl complexes with crown ether-containing PNP bisphosphines.

Figure 5 Comparison of heart/liver ratios between [^99mTcN(L4)(L6)]⁺ (^99mTcN-15C5), [^99mTcN(mpo)(PNP5)]⁺ (^99mTcN-MPO), [^99mTc(CO)₃(15CPNP)]⁺ (^99mTc-15C5PNP), ^99mTc-Sestamibi and ^99mTcN-DBODC5 in SD rats.

Figure 6 Planar images and organ clearance kinetics of normal dogs. A: Planar images of normal dogs administered with ^99mTcN-MPO and ^99mTc-Sestamibi. Both radiotracers had similar initial myocardial uptake; B: Imaging quantification in normal dogs administered with ^99mTcN-MPO; C: Imaging quantification in normal dogs administered with ^99mTc-Sestamibi. The liver radioactivity of ^99mTcN-MPO was markedly decreased within first 60 min whereas ^99mTc-Sestamibi had a slower reduction in liver radioactivity over time. A mild myocardial washout was observed in the dogs administered with ^99mTcN-MPO. No significant myocardial washout was seen in dogs administered with ^99mTc-Sestamibi.

Figure 7 SPECT images of the same dog (with acute myocardial infarction) administered with ~10 mCi of ^99mTc-Sestamibi and ^99mTcN-MPO at 30 and 60 min p. i. Arrows indicate the presence of perfusion defects due to myocardial infarction. For ^99mTcN-MPO, the perfusion defects were clearly seen as early as 30 min post-injection due to its fast liver clearance. For ^99mTc-Sestamibi, there was a significant between the perfusion defects and the liver radioactivity.

Figure 8 The whole-body images of representative a healthy volunteer administered with ^99mTcN-MPO. A: Administered with ^99mTcN-MPO (~25 mCi) at 10, 30, 60 and 240 min post-injection; B: Representative SPECT images of the heart after administration of ^99mTcN-MPO (~25 mCi) at 60 min post-injection.

Figure 9 Planar images of the SD rats administered with ~1. 0 mCi of ^99mTcN-MPO in the absence and presence of cyclosporin-A at 30 and 60 min post-injection. Pre-treatment with cyclosporin-A (14 mg/kg) results in more liver radioactivity accumulation and slower liver clearance.