Potential Myocardial Perfusion Imaging Agent Research Articles

Synthesis and Evaluation of (18)F-labeled Pyridaben Analogues for Myocardial Perfusion Imaging in Mice, Rats and Chinese mini-swine.

This study reports three novel 18F-labeled pyridaben analogues for potential myocardial perfusion imaging (MPI). Three precursors and the corresponding nonradioactive compounds were synthesized and characterized. The radiolabeled tracers were obtained by substituting tosyl with 18F. The total radiosynthesis time of these tracers was 70–90 min. Typical decay-corrected radiochemical yields were 47–58%, with high radiochemical purities (>98%). Tracers were evaluated as MPI agents in vitro, ex vivo and in vivo. In the mouse biodistribution study, all three radiotracers showed high initial heart uptake (34–54% ID/g at 2 min after injection) and fast liver clearance. In the microPET imaging study, [18F]Fmpp2 produced heart images with good quality in both mice and rats. In the whole-body PET/CT images of mini-swine, [18F]Fmpp2 showed excellent initial heart standardized uptake value (SUV) (7.12 at 5 min p.i.) and good retention (5.75 at 120 min p.i.). The heart/liver SUV ratios were 4.12, 5.42 and 5.99 at 30, 60 and 120 min after injection, respectively. The favorable biological properties of [18F]Fmpp2 suggest that it is worth further investigation as a potential MPI agent.

Synthesis, characterization and pre-clinical evaluation of99mTc-tricarbonyl complexes as potential myocardial perfusion imaging agents

Myocardial perfusion imaging is an established Nuclear Medicine investigation. Current myocardial perfusion imaging agents sestamibi and tetrofosmin have number of drawbacks; low heart uptake coupled with uptake into the surrounding tissues leads to a poorer image quality. There is a need for continued research into designing and evaluating potentially superior myocardial imaging agents. Tri-carbonyl-technetium and rhenium complexes were prepared by combination with mono-dentate and bi-dentate ligands. Complexes were characterized by HPLC, MAS, nuclear magnetic resonance, infrared, single-crystal X-ray diffraction and partition coefficient determinations. (99m) Tc(CO)3 complexes were administered intravenously to Sprague Dawley rats, and tissue distribution studies were carried out at 15 min and 1 h p.i. Radiochemical purity was assessed as >90%. 1-10-phenanthroline, 2,2'-bipyridine and imidazole complexes gave the highest heart uptake. The percentage injected dose per gram (n = 3) at 1 h for 1-10-phenanthroline/imidazole was blood 0.21 ± 0.01, heart 1.12 ± 0.11, kidney 3.61 ± 1.13, liver 0.62 ± 0.06, lung 0.28 ± 0.12, spleen 0.24 ± 0.05, small intestine contents 1.87 ± 0.92; and for 2,2'-bipyridine /imidazole was blood 0.23 ± 0.02, heart 1.07 ± 0.18, kidney 3.31 ± 1.28, liver 0.56 ± 0.09, lung 0.14 ± 0.02, spleen 0.2 ± 0.1, small intestine content 1.05 ± 0.48. Further investigation to evaluate more complexes based on 1,10-phenanthroline, 2,2'-bipyridine and imidazole derivatives could potentially lead to agents with an increased heart uptake and faster clearance from the liver and gastrointestinal tract.

Synthesis and biodistribution of a novel [99mTcN(PNP5)(DMCHDTC)]+ complex as a potential myocardial perfusion imaging agent

The [99mTcN(PNP5)(DMCHDTC)]+(DMCHDTC: 2,3-dimethyl cyclohexyl dithiocarbamate, PNP5:bis(dimethoxypropylphosphinoethyl)ethoxyethylamine) complex was synthesized through a ligand-exchange reaction. The two-step procedure involved the initial reaction of 99mTcO4− with succinic dihydrazide (SDH) as a donor of nitride nitrogen atom (N3−) in the presence of stannous chloride dihydrate as reducing agent and propylenediamine tetraacetic acid (PDTA) as complexant, followed by the addition of the PNP5 ligand and the DMCHDTC ligand. The radiochemical purity (RCP) of the product was over 90% as measured by thin layer chromatography (TLC). No decomposition of the complex at room temperature was observed over a period of 6h. Its partition coefficient indicated that it was a lipophilic complex. The electrophoresis results showed the complex was cationic. The biodistribution results in mice indicated that [99mTcN(PNP5)(DMCHDTC)]+ was significantly retained into the heart. The heart uptake (ID%/g) was 14.47, 12.23 and 8.76 at 5, 30 and 60min post-injection, respectively. The heart/liver, heart/lung and heart/blood ratios of the complex were 1.24, 3.62 and 23.05 at 60min post-injection, suggesting it will be a potential myocardial imaging agent.

Synthesis and biodistribution of 99mTcN-isopentyl xanthate as a potential myocardial perfusion imaging agent

A novel 99mTc nitrido xanthate complex 99mTcN(IPEXT)2 (IPEXT: isopentyl xanthate) has been synthesized by the reduction of 99mTcO4− into [99mTcN]2+ with stannous chloride in the presence of succinic dihydrazide and propylenediamine tetraacetic acid, followed by the addition of the corresponding xanthate ligand. The radiochemical purity of the complex was over 90% as measured by thin layer chromatography (TLC). No decomposition of the complex at room temperature was observed over a period of 6 hours. Its partition coefficient indicated that it was a lipophilic complex. The electrophoresis results showed the complex was neutral. Biodistribution in mice showed that the 99mTcN(IPEXT)2 complex accumulated in the heart with high uptake. The heart uptake (%IDg) was 8.00% at 5-minute post-injection, but the heart/lung, heart/liver and heart/blood ratios were not high, thereby, restricting the use of the complex as a good myocardial imaging agent.

99mTcN(PNP5)(NOEt)]+: A novel potential myocardial perfusion imaging agent

The asymmetrical [99mTcN(PNP5)(NOEt)]+heterocomplex containing a terminal technetium-nitrogen multiple bond coordinated to the diphosphine ligand (PNP5) and the dithiocarbamate ligand (NOEt), was prepared through ligand exchange reaction. Its radiochemical purity was over 90% as measured by TLC and HPLC. Biodistribution in mice and SPECT imaging in dog were studied. The results showed that [99mTcN(PNP5)(NOEt)]+ possessed high myocardial uptake and good retention, and high target to non-target ratios, suggesting that it may be a potential myocardial perfusion imaging agent.

Synthesis and biodistribution of 99mTcN(CHIPDTC)2 as a potential myocardial perfusion imaging agent

The bis(N-cyclohexyl, N-isopropyl dithiocarbamato) nitrido technetium-99m complex [99mTcN(CHIPDTC)2] (CHIPDTC: N-cyclohexyl, N-isopropyl dithiocarbamato) has been synthesized through a ligand-exchange reaction. The two-step procedure involved the initial reaction of 99mTcO4- with succinic dihydrazide (SDH) in the presence of stannous chloride as reducing agent and propylenediamine tetraacetic acid (PDTA) as complexant, followed by the addition of the sodium salt of N-cyclohexyl, N-isopropyl dithiocarbamate. The radiochemical purity (RCP) of the complex was 96±2% as measured by thin layer chromatography (TLC). No decomposition of the complex at room temperature (r. t.) was observed within a period of 6 hours. Its partition coefficient indicated that it was a lipophilic complex. The electrophoresis results showed that the complex was neutral. Biodistribution in mice indicated that the complex accumulated in the heart with high uptake and good retention. The heart/blood, heart/lung ratio was 6.28 and 1.35, respectively, at 60-minute post-injection, suggesting that it would be a potential myocardial perfusion imaging agent.

The chemistry of rhenium and technetium as related to the use of isotopes of these elements in therapeutic and diagnostic nuclear medicine

The β emitting isotopes 186Re and 188Re are logical choices on which to base therapeutic radiopharmaceuticals that might be expected to be analogous to diagnostic radiopharmaceuticals based on 99mTc. However, the chemistry of rhenium is sufficiently different from that of technetium so that the development of Re radiopharmaceuticals often cannot be predicated on the known chemistry and biological behavior of 99mTc radiopharmaceuticals. The relevant chemical differences involve the greater stability of the higher oxidation states of Re (and thus the greater tendency of reduced Re radiopharmaceuticals to undergo re-oxidation to perrhenate), and the greater substitution inertness of reduced Re complexes. These differences are illustrated (1) in the preparation and use of 186Re (Sn)-HEDP and 99mTc(Sn)-HEDP diphosphonate radiopharmaceuticals designed, respectively, for palliative therapy and diagnosis of metastatic cancer to bone, and (2) in the preparation and biodistribution of tr-[ 186Re(DMPE) 2Cl 2] + and [ 186Re(DMPE) 3] +, analogs to the potential myocardial perfusion imaging agents tr-[ 99mTc(DMPE) 2Cl 2] + and [ 99mTc(DMPE) 3] +. [HEDP = (1-hydroxyethylidene)diphosphonate; DMPE = 1,2-bis(dimethylphosphino)ethane].

Maximizing the information from thallium studies.

The clinical role of maximizing the value of T1-201 scintigraphy, both at rest and during a graded exercise tolerance test, as well as variations on that theme, have been described. Technical aspects of scintigraphy have been reviewed in view of the many complex properties of this radionuclide, including photon detection and attenuation. Rest studies may be important in acute myocardial infarction to predict complications, survival, and reoccurrence. The potential for stress testing has been emphasized, as well as the apparent problems of such studies in patients at high-risk, such as those with definite angina and post-coronary by-pass surgery. A comprehensive approach to the complementary or exclusionary nature of T1-201 (or other potential myocardial perfusion imaging agents) and ventricular function analysis using radionuclide techniques will be left to the present and future seers, which, of course, hopefully include this author and his associates.