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

Abstract

Background and purpose Anticancer therapy induces apoptosis in a dose- and time-dependent fashion. 99mTc-Hynic-rh-Annexin V scintigraphy (TAVS) enables non-invasive in vivo imaging of treatment-induced apoptosis. We identified the visual patterns of 99mTc-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 99mTc-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 (Δ U) 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 (Δ U range 1–3). Partial response ( n=7) was associated with weak to moderate U baseline and a moderately increased U post (Δ U 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 (Δ U range 0–1). Finally, in case of progressive disease ( n=2), either no tumour uptake or a decrease in U post was detected (Δ U=−1). A statistically significant correlation was found between changes in 99mTc-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 99mTc Hynic-rh-Annexin V accumulation early during treatment compared to baseline values. In case of stable or progressive disease, pretreatment scans demonstrated predominantly low 99mTc 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.