RT Journal Article
SR Electronic
T1 Imaging the intratumoral distribution of an EGFR-targeting antibody in a tumor mouse model using high-resolution focusing pinhole SPECT
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1566
OP 1566
VO 50
IS supplement 2
A1 Erwin Blezer
A1 Ruud Ramakers
A1 Jeroen van den Brakel
A1 Judith Oprins
A1 Frans van der Have
A1 Guus van Dongen
A1 Wim Bleeker
A1 Freek Beekman
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1566.abstract
AB 1566 Objectives Many tumor-targeting therapeutic human monoclonal antibodies (HMab) are evaluated in preclinical animal research. However the in vivo visualization of the intratumoral distribution may be hampered by resolution issues. A sub-half-mm resolution SPECT system with focused collimation was used to explore the tumor distribution of HMab directed to the Epidermal Growth Factor Receptor (EGFR). Methods 111In labeled EGFR-blocking HMab (Genmab, clone 2F8-IgG4, specific activity 0.5 MBq/µg, purity > 99%, immunoreactivity > 90%) were injected (t=0, i.v., 5 mg/kg, ~ 35 MBq) in SCID mice with subcutaneous A431 xenograft tumors of 1 ml. Whole body and local tumor SPECT images (U-SPECT-II, MIlabs, the Netherlands; 111In resolution 0.4 mm; Van der Have et al, JNM in press) were acquired at t=0 and 48 hrs, followed by CT (U-CT, MILabs). Results At t=0 111In-HMab were only present in the blood whereas at 48 hrs they were mainly located in the tumor with residual traces in blood and kidneys. This confirms the idea that antibody and 111In are internalized after tumor cell binding. High resolution tumor images showed that 111In-HMab were mainly located in the outer tumor rim confirming microscopic observations. Conclusions 111In labeled EGFR antibodies showed selective tumor uptake 48 hrs after administration. High resolution SPECT imaging revealed intratumoral distribution differences. High resolution SPECT imaging is a powerful tool to correlate antibody distribution with histological tumor features.