Detection of Dose Response in Chronic Doxorubicin-Mediated Cell Death with Cardiac Technetium 99m Annexin V Single-Photon Emission Computed Tomography

The aim of this study was to evaluate whether technetium 99m hydrazinonicotinamide ( 99m Tc-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 Sprag...

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Main Authors: Kathleen L. Gabrielson, Greta S.P. Mok, Srihdar Nimmagadda, Djahida Bedja, Scott Pin, Allison Tsao, Yuchuan Wang, Dhrtti Sooryakumar, S. Jianhua Yu, Martin G. Pomper, Benjamin M.W. Tsui
Format: Article
Language:English
Published: SAGE Publishing 2008-05-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2008.00015
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author Kathleen L. Gabrielson
Greta S.P. Mok
Srihdar Nimmagadda
Djahida Bedja
Scott Pin
Allison Tsao
Yuchuan Wang
Dhrtti Sooryakumar
S. Jianhua Yu
Martin G. Pomper
Benjamin M.W. Tsui
author_facet Kathleen L. Gabrielson
Greta S.P. Mok
Srihdar Nimmagadda
Djahida Bedja
Scott Pin
Allison Tsao
Yuchuan Wang
Dhrtti Sooryakumar
S. Jianhua Yu
Martin G. Pomper
Benjamin M.W. Tsui
author_sort Kathleen L. Gabrielson
collection DOAJ
description The aim of this study was to evaluate whether technetium 99m hydrazinonicotinamide ( 99m Tc-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 99m Tc-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 99m Tc-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 99m Tc-HYNIC-annexin V detects dose-dependent cell death before ventricular deficits are observed with echocardiography. 99m Tc-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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spelling doaj-art-e6d86c528b874fc18c23578e01fd3b1f2025-02-03T10:08:01ZengSAGE PublishingMolecular Imaging1536-01212008-05-01710.2310/7290.2008.0001510.2310_7290.2008.00015Detection of Dose Response in Chronic Doxorubicin-Mediated Cell Death with Cardiac Technetium 99m Annexin V Single-Photon Emission Computed TomographyKathleen L. GabrielsonGreta S.P. MokSrihdar NimmagaddaDjahida BedjaScott PinAllison TsaoYuchuan WangDhrtti SooryakumarS. Jianhua YuMartin G. PomperBenjamin M.W. TsuiThe aim of this study was to evaluate whether technetium 99m hydrazinonicotinamide ( 99m Tc-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 99m Tc-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 99m Tc-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 99m Tc-HYNIC-annexin V detects dose-dependent cell death before ventricular deficits are observed with echocardiography. 99m Tc-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.https://doi.org/10.2310/7290.2008.00015
spellingShingle Kathleen L. Gabrielson
Greta S.P. Mok
Srihdar Nimmagadda
Djahida Bedja
Scott Pin
Allison Tsao
Yuchuan Wang
Dhrtti Sooryakumar
S. Jianhua Yu
Martin G. Pomper
Benjamin M.W. Tsui
Detection of Dose Response in Chronic Doxorubicin-Mediated Cell Death with Cardiac Technetium 99m Annexin V Single-Photon Emission Computed Tomography
Molecular Imaging
title Detection of Dose Response in Chronic Doxorubicin-Mediated Cell Death with Cardiac Technetium 99m Annexin V Single-Photon Emission Computed Tomography
title_full Detection of Dose Response in Chronic Doxorubicin-Mediated Cell Death with Cardiac Technetium 99m Annexin V Single-Photon Emission Computed Tomography
title_fullStr Detection of Dose Response in Chronic Doxorubicin-Mediated Cell Death with Cardiac Technetium 99m Annexin V Single-Photon Emission Computed Tomography
title_full_unstemmed Detection of Dose Response in Chronic Doxorubicin-Mediated Cell Death with Cardiac Technetium 99m Annexin V Single-Photon Emission Computed Tomography
title_short Detection of Dose Response in Chronic Doxorubicin-Mediated Cell Death with Cardiac Technetium 99m Annexin V Single-Photon Emission Computed Tomography
title_sort detection of dose response in chronic doxorubicin mediated cell death with cardiac technetium 99m annexin v single photon emission computed tomography
url https://doi.org/10.2310/7290.2008.00015
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