A novel clinical indicator using cardiac technetium-99m sestamibi kinetics for evaluating cardiotoxicity in cancer patients treated with multiagent chemotherapy

Abstract

Background: Multiagent chemotherapy (MCT) has mitochondrial targets. Since technetium-99m-sestamibi (MIBI) is a marker of mitochondrial metabolism, cardiac MIBI uptake and MIBI washout rate (%WR) may detect MCT-induced cardiotoxicity.

Methods: In 16 cancer patients on MCT for 10 months and in 14 non-cancer controls, cardiac MIBI uptake between early (30 min) and delayed (3 hours) post-injection planar images was measured as counts per pixel (cpp). The MIBI cardiac %WR was also measured.

Results: When MCT patients and controls were compared, early and cardiac delayed MIBI uptake were greater in MCT patients (45 ± 12 cpp vs. 30 ± 4 cpp; p <0.04) and (30 ± 8 cpp vs. 25 ± 2 cpp; p < 0.02), but % WR did not change (12 ± 4% vs. 13 ± 3%; p = ns). However, in the MCT patients, the MIBI cardiac %WR was more rapid because it was obtained at the same time as in the control patients but from a greater amount of MIBI cardiac uptake. On 36-months follow-up, only MCT patients died of cardiac death. Overall survival risk parameters, only delayed cardiac MIBI uptake (Odds ratio = 1.7, p<0.001) and early cardiac MIBI uptake (Odds ratio = 1.2, p<0.02) were found to be significantly associated with cardiac mortality.

Conclusions: In experimental studies, anticancer drugs elicit mitochondrial membrane hyperpolarization with passive cardiac MIBI uptake. In MCT patients, the increased cardiac MIBI uptake and rapid %WR compared with controls may reflect mitochondrial membrane dysfunction, pre-clinical cardiotoxicity and thus poor prognosis.

Keywords: Multiagent chemotherapy (MCT); cancer; cardiotoxicity; mitochondrial metabolism; multiagent chemotherapy; technetium-99m-sestamibi (MIBI).

Figure 1

A. early (e) planar imaging 30 min after MIBI injection. B. delayed (d) planar imaging 3 hours after MIBI injection. ROIs for MIBI uptake calculation are shown: cardiac (red arrows), site of injection (green arrows), and liver (white arrows).

Figure 2

MIBI SPECT of a patient after MCT. An inferior reversible defect (white arrows) and a lateral reversible defect (red arrow) are shown. A coronary angiogram revealed an absence of coronary obstructions.

Figure 3

Kaplan-Meier curves; delayed (d) cardiac MIBI uptake values stratified individuals with respect to mortality.