Key result
99m Tc-(HE)₃-(GPO)₉ SPECT/CT imaging reveals higher tracer uptake in the infarct zone of MI mice.
Why the study?
Existing imaging techniques detect established fibrotic changes but lack sensitivity for ongoing collagen turnover after myocardial infarction.
Does the radiotracer 99m Tc-(HE)₃-(GPO)₉ enable non-invasive detection of denatured collagen as a marker of collagen turnover after myocardial infarction?
Does the radiotracer 99m Tc-(HE)₃-(GPO)₉ enable non-invasive detection of denatured collagen as a marker of collagen turnover after myocardial infarction?
p-value: p=<0.0001
99m Tc-(HE)₃-(GPO)₉ enables non-invasive molecular imaging of denatured collagen, providing a potential tool for assessing fibrotic remodeling after myocardial infarction.
Tracer uptake distinguishes infarct collagen in mice; hypothesis-generating for clinical fibrosis imaging.
Cardiac fibrosis is a key contributor to cardiomyopathy after myocardial infarction (MI). Existing imaging techniques can detect established fibrotic changes; however, they lack sensitivity for ongoing collagen turnover—a dynamic process involving the denaturation of collagen triple helix. Molecular imaging of this process could enhance risk assessment and aid in the development of anti-fibrotic treatments. This study aimed to evaluate 99m Tc-(HE)₃-(GPO)₉, a radiotracer designed to target denatured collagen, as a biomarker of collagen turnover after MI. Methods 99m Tc-(HE)₃-(GPO)₉ incorporates glycine-proline-hydroxyproline (GPO) repeats and can hybridize with denatured single- or double-stranded collagen. MI was induced in mice by ligation of the left anterior descending artery; sham-operated animals served as controls. At 2 weeks post-MI, animals underwent myocardial perfusion imaging or contrast-enhanced CT to detect the infarct zone, followed by SPECT/CT imaging using 99m Tc-(HE)₃-(GPO)₉ or a control scrambled tracer. Tracer uptake was quantified in vivo and ex vivo with gamma counting and autoradiography. Different aspects of fibrosis were examined by tissue analysis, along with autoradiography with a matrix metalloproteinase-targeted radiotracer, 99m Tc-RYM1. Tracer binding was also assessed in human cardiac tissue through ex vivo autoradiography. Results 99m Tc-(HE)₃-(GPO)₉ SPECT/CT revealed significantly higher tracer uptake in the infarct zone of MI mice compared to the remote zone and sham controls (P < 0.0001 for both). Tracer uptake was confirmed by autoradiography, which showed a strong correlation between SPECT and autoradiography (R = 0.81, P < 0.01). The scrambled tracer exhibited minimal cardiac uptake, demonstrating the specificity of 99m Tc-(HE)₃-(GPO)₉ signal. Denatured collagen staining and 99m Tc-RYM1 autoradiography showed similar patterns as ex vivo 99m Tc-(HE)₃-(GPO)₉ autoradiography, while the ratio of denatured collagen to procollagen in the infarct zone significantly increased from day 3 to 2 weeks post-MI. Finally, 99m Tc-(HE)₃-(GPO)₉ bound to human fibrotic (but not normal) cardiac tissue. Conclusion 99m Tc-(HE)₃-(GPO)₉ enables non-invasive detection of denatured collagen as a marker of collagen remodeling in vivo, offering a promising tool for assessing fibrotic remodeling after MI. Collagen, procollagen, and denatured collagen, along with MMP activation, exhibit distinct patterns, and their combined imaging may provide a comprehensive molecular fingerprint of cardiac fibrosis, advancing personalized management of cardiomyopathy.
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Neishabouri et al. (2026) studied Myocardial Infarction and Cardiac Fibrosis. 99m Tc-(HE)₃-(GPO)₉ radiotracer imaging vs. Sham-operated controls and scrambled tracer was evaluated on Tracer uptake in the infarct zone (p=<0.0001). 99m Tc-(HE)₃-(GPO)₉ SPECT/CT imaging revealed significantly higher tracer uptake in the infarct zone of MI mice compared to the remote zone and sham controls (P < 0.0001).
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