99mTc-HYNIC-rh-annexin-V scintigraphy: visual and quantitative evaluation of early treatment-induced apoptosis to predict treatment outcome

Abstract

To determine the reliability of visual analysis of 99mTc-HYNIC-rh-annexin-V tumour uptake (ATU) compared to quantitative tracer uptake evaluation. Thirty-eight patients (22 male, 16 female, mean age 57) with histologically proved lymphoma (n=31), non-small cell lung cancer (NSCLC) (n=4) and head and neck squamous cell carcinoma (H&NSCC) (n=3) were examined. 99mTc-HYNIC-rh-annexin-V scintigraphy (TAS) was acquired before and within 2 days after the start of anti-cancer treatment. Maximal counts per pixel in the tumour volume (Cmax) were calculated for every target lesion. To match the quantitative and visual ATU, both were expressed as a four-grade score. Cmax as percentages of baseline values: grade 1, decrease >25%; grade 0, 1-25% decrease; grade 1, 1-25% increase; grade 2, >25% increase. Visual analysis: 0=absent, 1=weak, 2=moderate, 3=intense. Intra-observer and inter-observer variability and methodological agreement between visual and quantitative evaluation of ATU was expressed by computing Cohen's kappa statistics. A statistically highly significant correlation was found between the changes in ATU and therapy outcome: r=0.97 (P<0.0001) and r=0.99 (P<0.0001) for visual and quantitative analysis, respectively. Good intra-observer reproducibility, with a high kappa of 0.82 for observer 1 and a kappa of 0.90 for observer 2, was determined. Inter-observer variability was 0.82. Visual evaluation of ATU after image co-registration appears to be a reliable and reproducible method for preliminary assessment of early treatment-induced apoptosis.