Key result
99mTc-HYNIC-annexin V SPECT detects doxorubicin-induced cardiac cell death before ventricular deficits appear on echocardiography.
Why the study?
The ability of 99mTc-HYNIC-annexin V SPECT to detect dose-dependent doxorubicin-mediated cardiac cell death compared with functional echocardiography was evaluated.
Does 99mTc-HYNIC-annexin V SPECT detect dose-dependent doxorubicin-mediated cell death in the heart earlier than functional echocardiography in a rat model?
Does 99mTc-HYNIC-annexin V SPECT detect dose-dependent doxorubicin-mediated cell death in the heart earlier than functional echocardiography in a rat model?
99mTc-HYNIC-annexin V SPECT imaging can detect early dose-dependent doxorubicin-induced cardiac toxicity before functional deficits are apparent on echocardiography.
May enable earlier doxorubicin cardiotoxicity detection than echocardiography; leaves open human translation and clinical adoption.
The aim of this study was to evaluate whether technetium 99m hydrazinonicotinamide (99mTc-HYNIC)-annexin V single-photon emission computed tomography (SPECT) would detect dose-dependent doxorubicin (DOX)-mediated cell death in the heart compared with functional echocardiography. Adult female Sprague-Dawley rats were treated with DOX (cumulative dose of 15 or 7.5 mg/kg) or saline (n = 7) and monitored by echocardiography. Rats were injected with 7 to 8 mCi 99mTc-HYNIC-annexin V and imaged 1 hour postinjection using a small animal dual-head SPECT/computed tomography (CT) system with multipinhole technology. Two regions of interest were drawn in the myocardium and soft tissue regions to calculate the cardiac uptake ratio (CUR) of reconstructed images. Myocardium and blood were harvested for radioactivity measurements or TUNEL assay. Biodistribution of 99mTc-HYNIC-annexin V uptake, CUR from SPECT/CT fused cardiac images, and TUNEL of myocardium demonstrated a dose-dependent toxicity response, with the cumulative 15 mg/kg DOX treatment showing the greatest degree of cell death. In contrast, echocardiography detected functional deficits only at the highest DOX dose. In vivo molecular imaging of DOX-induced cardiac toxicity with 99mTc-HYNIC-annexin V detects dose-dependent cell death before ventricular deficits are observed with echocardiography. 99mTc-HYNIC-annexin V SPECT-based molecular imaging may provide an attractive new technique for assessing early changes in myocardial function in patients undergoing DOX therapy.
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Gabrielson et al. (2008) studied Doxorubicin-induced cardiac toxicity. 99mTc-HYNIC-annexin V SPECT vs. functional echocardiography was evaluated on dose-dependent doxorubicin-mediated cell death. 99mTc-HYNIC-annexin V SPECT detected dose-dependent doxorubicin-induced cardiac cell death before ventricular deficits were observed with echocardiography.
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