Detection of anthracycline-induced cardiotoxicity using perfusion-corrected 99mTc sestamibi SPECT

TY - JOUR

T1 - Detection of anthracycline-induced cardiotoxicity using perfusion-corrected 99mTc sestamibi SPECT

AU - Safee, Zaitulhusna M.

AU - Baark, Friedrich

AU - Waters, Edward C. T.

AU - Veronese, Mattia

AU - Pell, Victoria R.

AU - Clark, James E.

AU - Mota, Filipa

AU - Livieratos, Lefteris

AU - Eykyn, Thomas R

AU - Blower, Philip J.

AU - Southworth, Richard

PY - 2019

Y1 - 2019

N2 - By the time cardiotoxicity-associated cardiac dysfunction is detectable by echocardiography it is often beyond meaningful intervention. 99mTc-sestamibi is used clinically to image cardiac perfusion by single photon emission computed tomography (SPECT) imaging, but as a lipophilic cation its distribution is also governed by mitochondrial membrane potential (ΔΨm). Correcting scans for variations in perfusion (using a ΔΨm-independent perfusion tracer such as (bis(N-ethoxy-N-ethyldithiocarbamato)nitrido 99mTc(V)) (99mTc-NOET) could allow 99mTc-sestamibi to be repurposed to specifically report on ΔΨm as a readout of evolving cardiotoxicity. Isolated rat hearts were perfused within a γ-detection apparatus to characterize the pharmacokinetics of 99mTc-sestamibi and 99mTc-NOET in response to mitochondrial perturbation by hypoxia, ionophore (CCCP) or doxorubicin. All interventions induced 99mTc-sestamibi washout; hypoxia from 24.9 ± 2.6% ID to 0.4 ± 6.2%, CCCP from 22.8 ± 2.5% ID to −3.5 ± 3.1%, and doxorubicin from 23.0 ± 2.2% ID to 17.8 ± 0.7, p 

AB - By the time cardiotoxicity-associated cardiac dysfunction is detectable by echocardiography it is often beyond meaningful intervention. 99mTc-sestamibi is used clinically to image cardiac perfusion by single photon emission computed tomography (SPECT) imaging, but as a lipophilic cation its distribution is also governed by mitochondrial membrane potential (ΔΨm). Correcting scans for variations in perfusion (using a ΔΨm-independent perfusion tracer such as (bis(N-ethoxy-N-ethyldithiocarbamato)nitrido 99mTc(V)) (99mTc-NOET) could allow 99mTc-sestamibi to be repurposed to specifically report on ΔΨm as a readout of evolving cardiotoxicity. Isolated rat hearts were perfused within a γ-detection apparatus to characterize the pharmacokinetics of 99mTc-sestamibi and 99mTc-NOET in response to mitochondrial perturbation by hypoxia, ionophore (CCCP) or doxorubicin. All interventions induced 99mTc-sestamibi washout; hypoxia from 24.9 ± 2.6% ID to 0.4 ± 6.2%, CCCP from 22.8 ± 2.5% ID to −3.5 ± 3.1%, and doxorubicin from 23.0 ± 2.2% ID to 17.8 ± 0.7, p 

UR - http://www.scopus.com/inward/record.url?scp=85060142431&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-36721-5

DO - 10.1038/s41598-018-36721-5

M3 - Article

C2 - 30659226

SN - 2045-2322

VL - 9

SP - 216

EP - 227

JO - Scientific Reports

JF - Scientific Reports

M1 - 216

ER -