RT Journal Article
SR Electronic
T1 Assessment of cell apoptosis using radiolabeled EC-TRAIL antibody
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 345P
OP 345P
VO 48
IS supplement 2
A1 Saady Kohanim
A1 David Yang
A1 Razelle Kurzrock
A1 Bryant Jerry
A1 Dong-Fang Yu
A1 Hiroaki Kurihara
A1 Ning Tsao
A1 Chang-Sok Oh
A1 E. Edmund Kim
YR 2007
UL http://jnm.snmjournals.org/content/48/supplement_2/345P.3.abstract
AB 1495 Objectives: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as Apo-2L, is a potent promoter of programmed cell death in diverse tumor types. TRAIL binds to a family of receptors including death receptors 4 and 5 (TR1 and TR2). This study was aimed to image mice bearing human colorectal (colo205) tumors using Tc-99m and/or In-111 labeled ethylenedicysteine–TR1 (EC-TR1) antibody and EC-TR2 antibody. The imaging findings were correlated with immunoblotting expression of ETR1 and ETR2. Methods: Both TR1 and Tr2 antibodies were conjugated with EC using carbodiimide as a coupling agent. Athymic nude mice were inoculated intramuscularly with Colo205 cell suspensions. To ascertain cell apoptosis, paclitaxel treatment (60mg/kg i.v. in tail vein) was performed 10 to 14 days after inoculation when tumor had grown to 1cm in diameter. Planar gamma camera imaging studies and autoradiograms of In-111 labeled EC-TR1 and EC-TR2 were conducted at pre- and post-paclitaxel treatment. In-111-EC-IgG1 was used as a control. Tumors were incised at 24 or 48 hrs after paclitaxel treatment. Immunoblots with antibodies of anti-TRAIL-R1, anti-TRAIL-R2, anti-p53, anti-phospho-p53 (Ser15), anti-Erk1/2 and anti-phospho-Erk1/2 (Thr202/Tyr 204) were performed. Results: Paclitaxel significantly increased in vivo expression of TR1 and TR2 in a time-dependent manner. There was an increased uptake of In-111 labeled EC-TR1 and EC-TR2 antibodies in Colo205 tumor tissue at 24 hrs after paclitaxel treatment. The imaging results correlate well with immunoblots findings for steady-state protein levels (over 20-fold increase in TR1 and TR2 levels in tumor xenografts by 48 hours post-paclitaxel administration). TR1 and TR2 mRNA expression was not changed, suggesting that these effects were post-transcriptional. Conclusions: Radiolabeled EC-TR1 and EC-TR2 could assess the effects of auto-amplification of cell apoptosis on anti-cancer therapy in vivo.