Evaluation of 99mTechnetium-Vancomycin Imaging Potential in Experimental Rat Model for the Diagnosis of Infective Endocarditis

Background: Infective endocarditis (IE) is an infection of the heart’s endocardial surface. In recent years, nuclear imaging methods have gained importance in the diagnosis of IE. The present study aims to investigate the imaging potential of 99mTc-labeled vancomycin ( 99mTc-Vancomycin) as a new agent that would enable the diagnosis of IE in its early stages when it is difficult to diagnose or has small vegetation, in the experimental rat model. Methods: 99mTc-Vancomycin scintigraphy was evaluated for its accumulation in IE with Staphylococcus aureus performed in an experimental rat model. Serial planar scintigraphic and biodistribution analysis of infected vegetations are compared to rats with sterile vegetations. The heart was identified as an infected organ, the liver was identified as a noninfected organ and the heart/liver uptake ratio (T / NT ratio) was compared between infective endocarditis and sterile endocarditis groups. Results: Planar scintigrams (in vivo measurements) showed more uptake in the heart of rats in the infective endocarditis group, compared to the uptake in the heart of rats in the sterile endocarditis group but this difference was not statistically significant (p>0.05). From the ex vivo measurements, the 99mTc-Vancomycin heart uptake increased significantly (p = 0.016), liver uptake was significantly decreased (p = 0.045) and the T/NT ratio was significantly higher (p = 0.014) in the infective endocarditis group compared to the sterile endocarditis group. Conclusions: In this experimental study, 99mTc-Vancomycin scintigraphy ensured the detection of ex vivo infected tissue in a rat model of IE. In addition, the absence of significant 99mTc-Vancomycin uptake in the sterile endocarditis group indicates that this agent targeted the infected tissue instead of the sterile inflammatory tissue. Finally, this agent should also be evaluated with animal-specific imaging devices.

Cysteine Derivatized 99mTc-Labelled Fatty Acids as β-Oxidation Markers

With the aim of developing 99mTc-labeled fatty acids intended for myocardial metabolism imaging we report herein the synthesis and characterization of two novel derivatives of undecanonoic and hexadecanonoic acid that have been functionalized at the ω-site by cysteine through the formation of a thioether bond (Cys–FA11 and Cys–FA16). Equimolar amounts of each ligand and the [NEt4]2[Re(CO)3Br3] precursor generated the respective hexacoordinated neutral complexes in which the ligand coordinated to the metal through the SNO donor system of cysteine. The rhenium complexes were characterized by elemental analysis, IR and NMR spectroscopies. The analogous technetium-99m complexes, 99mTc–Cys–FA11 and 99mTc–Cys–FA16 were prepared by incubation of the ligand with the precursor [99mTc(CO)3(H2O)3]+ (radiochemical yield ≥98%). Their structure was established by comparative HPLC techniques. In vivo studies in mice showed high initial heart uptake for both 99mTc complexes (7.4 ± 0.53 and 7.07 ± 0.73 percentage of injected dose (%ID)/g at 1 min post injection. Rapid clearance (0.60 ± 0.02 %ID/g) was observed for 99mTc–Cys–FA11 while the clearance of the longer fatty acid 99mTc–Cys–FA16 was slower (2.31 ± 0.09 %ID/g at 15 min p.i.). Metabolite analysis study indicated that complexes were catabolized through the β-oxidation process.

New 99mTc Radiotracers for Myocardial Perfusion Imaging by SPECT

Objective: Myocardial Perfusion Imaging (MPI) with radiotracers is an integral component in evaluation of the patients with known or suspected coronary artery diseases (CAD). 99mTc-Sestamibi and 99mTc-Tetrofosmin are commercial radiopharmaceuticals for MPI by single photon-emission computed tomography (SPECT). Despite their widespread clinical applications, they do not meet the requirements of an ideal perfusion imaging agent due to their inability to linearly track the regional myocardial blood flow rate at >2.5 mL/min/g. With tremendous development of CZT-based SPECT cameras over the past several years, the nuclear cardiology community has been calling for better perfusion radiotracers with improved extraction and biodistribution properties. Methods: This review will summarize recent research efforts on new cationic and neutral 99mTc radiotracers for SPECT MPI. The goal of these efforts is to develop a 99mTc radiotracer that can be used to detect perfusion defects at rest or under stress, determine the regional myocardial blood flow, and measure the perfusion and left ventricular function. Results: The advantage of cationic radiotracers (e.g. 99mTc-Sestamibi) is their long myocardial retention because of the positive molecular charge and fast liver clearance kinetics. 99mTc-Teboroxime derivatives have a high initial heart uptake (high first-pass extraction fraction) due to their neutrality. 99mTc- 3SPboroxime is the most promising radiotracer for future clinical translation considering its initial heart uptake, myocardial retention time, liver clearance kinetics, heart/liver ratios and SPECT image quality. Conclusion: 99mTc-3SPboroximine is an excellent example of perfusion radiotracers, the heart uptake of which is largely relies on the regional blood flow. It is possible to use 99mTc-3SPboroximine for detection of perfusion defect(s), accurate quantification and determination of regional blood flow rate. Development of such a 99mTc radiotracer is of great clinical benefit for accurate diagnosis of CAD and assessing the risk of future hard events (e.g. heart attack and sudden death) in cardiac patients.

Radioiodination and biological evaluation of landiolol as a tracer for myocardial perfusion imaging: preclinical evaluation and diagnostic nuclear imaging

The present work has assessed the ability and competency of radioiodinated landiolol that is considered a potential cardio selective imaging agent. Landiolol was radiosynthesized with [131I] using chloramine-T (Ch-T) as an oxidizing agent. To give high radiochemical yield of the [131I]landiolol reaching values of 98% with high stability up to 48 h. The labeled compound was separated and purified using thin layer chromatography (TLC), paper electrophoresis and high performance liquid chromatography (HPLC). Biodistribution studies indicated that [131I]landiolol gave high heart uptake ratio of [45.0±0.19% ID/g at 2 min post injection (p.i.)]. Therefore, [131I]landiolol could be considered as a novel tracer to image heart with high heart/blood ratio within 60 min.

99mTc-3Cboroxime: a novel 99mTc(iii) complex [99mTcCl(CDO)(CDOH)2B-3C] (CDOH2 = cyclohexanedione dioxime; 3C-B(OH)2 = 3-(carbamoylphenyl)boronic acid) with high heart uptake and long myocardial retention

In this study, we found that 99mTc-3Cboroxime has the myocardial retention longer than that of 99mTc-Teboroxime, and its heart washout kinetics follows a regressive linear relationship over the 60 min period.