RT Journal Article
SR Electronic
T1 99mTc-Annexin-V and 99mTc-Sestamibi uptake as indicators of chemotherapy induced apoptosis.
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1575
OP 1575
VO 50
IS supplement 2
A1 Paola Anna Erba
A1 Enrica Tusi
A1 Chiara Manfredi
A1 Maria Teresa Locci
A1 Martina Sollini
A1 Elena Lazzeri
A1 Katrin Massri
A1 Luisa Locantore
A1 Giuliano Mariani
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1575.abstract
AB 1575 Objectives 99mTc-Annexin-V can be employed to monitor apoptosis in vivo.99mTc-Sestamibi has been shown to be inversely correlated with levels of Bcl-2: reduction of 99mTc-Sestamibi uptake in response to an antiblastic agent would reflect resistance to apoptosis.We evaluated 99mTc-Annexin V and 99mTc-Sestamibi uptake in a virus-induced model of mouse breast cancer . Methods Biodistribution was evaluated in tumor-bearing mice in baseline conditions and 1, 3, 6 and 24 hr after 0.02 mg/g bw Paclitaxel given iv.Biodistribution was assessed 1 hr after injection of 99mTc-Annexin V and 20 min after 99mTc-Sestamibi.Tumour samples were also processed by WB and IF to identify apoptotic cells (TUNEL) and expression of Caspase-3, Caspase-8 and Bcl-2. Results A highly significant correlation between 99mTc-Annexin V and 99mTc-Sestamibi with a peak 3-hr uptake was found,suggesting that they both may be used as indicators of apoptosis.TUNEL was significantly correlated with uptake of both 99mTc-Annexin V (p<0.0001) and 99mTc-Sestamibi (p=0.0122).Caspase-3 and -8 expression was prevalent in baseline condition and 6-24 hr after treatment, while Bcl-2 was high in baseline condition, reached a nadir at 3 hr and subsequent recovered. Conclusions These observations confirm the anti-apoptotic role of Bcl-2 and suggest the co-existence of two apoptotic cell populations: an early apoptotic response probably mediated by Caspase-10 and a later, minor apoptotic event mediated by Caspase-3.