In vivo imaging of apoptosis by 99mTc-annexin V scintigraphy:: visual analysis in relation to treatment response

Background and purpose: Anticancer therapy induces apoptosis in a dose- and time-dependent fashion. Tc-99m-Hynic-rh-Annexin V scintigraphy (TAVS) enables non-invasive in vivo imaging of treatment-induced apoptosis. We identified the visual patterns of Tc-99m-Hynic-rh-Annexin V tumour uptake and related these to treatment response. Patients and methods: Thirty-three patients with malignant lymphoma (n = 26), leukaemia (n = 1) NSCLC (n = 5), H&NSCC (n = 1), scheduled for radiotherapy (n = 27), platinum-based chemotherapy (n = 5) or concurrent chemoradiation (n = 1), underwent TAVS before and early after the start of treatment. Planar and SPECT images were visually examined to assess changes in tumour Tc-99m-Hynic-rh-Annexin V uptake. Twenty-nine patients were eligible for further analysis. Annexin V uptake before (U-baseline) and early after (U-post) the start of treatment was graded using a four-step scale: 0, absent; 1, weak; 2, moderate and 3, intense. The difference between these values (DeltaU) was calculated and correlated to tumour response after therapy (Spearman rank correlation test). Results: Weak to moderate U-baseline was detected in 13/15 patients with a complete response and U-post was markedly increased in all these cases (DeltaU range 1-3). Partial response (n=7) was associated with weak to moderate U-baseline and a moderately increased U-post (DeltaU range 1-2). In patients with stable disease (n=5), U-baseline was predominantly weak, without considerable changes in uptake after the start of treatment (DeltaU range 0-1). Finally, in case of progressive disease (n=2), either no tumour uptake or a decrease in U-post was detected (DeltaU=-1). A statistically significant correlation was found between changes in Tc-99m-Hynic-rh-Annexin V tumour uptake and clinical response (correlation coefficient=0.62; P<0.001). Conclusions: Complete or partial tumour response was associated with a marked increase of Tc-99m Hynic-rh-Annexin V accumulation early during treatment compared to baseline values. In case of stable or progressive disease, pretreatment scans demonstrated predominantly low Tc-99m Hynic-rh-Annexin V tumour uptake and no significant increase early after treatment. These results indicate that TAVS might be useful as a predictive test for treatment response. (C) 2004 Elsevier Ireland Ltd. All rights reserved.