Assessment of Chemotherapy-Induced Organ Damage with Ga-68 Labeled Duramycin.

PURPOSE: Evaluation of [68Ga]NODAGA-duramycin as a positron emission tomography (PET) tracer of cell death for whole-body detection of chemotherapy-induced organ toxicity. PROCEDURES: Tracer specificity of Ga-68 labeled NODAGA-duramycin was determined in vitro using competitive binding experiments. Organ uptake was analyzed in untreated and doxorubicin, busulfan, and cisplatin-treated mice 2 h after intravenous injection of [68Ga]NODAGA-duramycin. In vivo data were validated by immunohistology and blood parameters. RESULTS: In vitro experiments confirmed specific binding of [68Ga]NODAGA-duramycin. Organ toxicities were detected successfully using [68Ga]NODAGA-duramycin PET/X-ray computed tomography (CT) and confirmed by immunohistochemistry and blood parameter analysis. Organ toxicities in livers and kidneys showed similar trends in PET/CT and immunohistology. Busulfan and cisplatin-related organ toxicities in heart, liver, and lungs were detected earlier by PET/CT than by blood parameters and immunohistology. CONCLUSION: [68Ga]NODAGA-duramycin PET/CT was successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in mice. It, therefore, represents a promising alternative to standard toxicological analyses with a high translational potential.

Strain rate measurement by doppler echocardiography allows improved assessment of myocardial viability inpatients with depressed left ventricular function.

OBJECTIVES: This study sought to evaluate whether objective assessment of the myocardial functional reserve, using strain rate imaging (SRI), allows accurate detection of viable myocardium. BACKGROUND: Strain rate imaging is a new echocardiographic modality that allows quantitative assessment of segmental myocardial contractility. METHODS: In 37 patients (age 58 +/- 9 years) with ischemic left ventricular dysfunction, myocardial viability was assessed using low-dose (10 microg/kg body weight per min) two-dimensional dobutamine stress echocardiography (DSE), tissue Doppler imaging, SRI and (18)F-fluorodeoxyglucose ((18)FDG) positron emission tomography (PET). The peak systolic tissue Doppler velocity and peak systolic myocardial strain rate were determined at baseline and during low-dose dobutamine stress from the apical views. RESULTS: A total of 192 segments with dyssynergy at rest were classified by (18)FDG PET as viable in 94 and nonviable in 98. An increase of peak systolic strain rate from rest to dobutamine stimulation by more than -0.23 1/s allowed accurate discrimination of viable from nonviable myocardium, as determined by (18)FDG PET with a sensitivity of 83% and a specificity of 84%. Receiver operating characteristic (ROC) curve analysis showed an area under the curve for prediction of nonviable myocardium, as determined by (18)FDG PET using SRI, of 0.89 (95% confidence interval [CI] 0.88 to 0.90), whereas the area under the ROC curve using tissue Doppler imaging was 0.63 (95% CI 0.61 to 0.65). CONCLUSIONS: The increase in the peak systolic strain rate during low-dose dobutamine stimulation allows accurate discrimination between different myocardial viability states. Strain rate imaging is superior to two-dimensional DSE and tissue Doppler imaging for the assessment of myocardial viability.