RT Journal Article
SR Electronic
T1 Preclinical development of Zr-89 labeled anti-PSMA minibody and cys-diabody
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 347
OP 347
VO 53
IS supplement 1
A1 Viola-Villegas, Nerissa
A1 Evans, Henry
A1 Bartlett, Derek
A1 Wu, Anna
A1 Lewis, Jason
YR 2012
UL http://jnm.snmjournals.org/content/53/supplement_1/347.abstract
AB 347 Objectives Antibody-based imaging needs optimization due to slow targeting and tumor uptake. In contrast, engineered antibody fragments, retain the properties of antibodies with rapid delivery and clearance from the bloodstream and normal tissues. Here, we employed two engineered antibody fragments, known as a minibody (~80 kDa, Mb) and a Cys-diabody (~50 kDa, Cys-Db), as radiotracers with high-affinity binding to the prostate-specific membrane antigen (PSMA) that is over-expressed on prostate cancer cells. Methods We functionalized these proteins with deferoxamine and labeled with Zr-89. Specific activities range from 6.0-8.0 mCi/mg with radiochemical yields of >70% for both proteins. Immunoreactivities of the Mb and Cys-Db were retained at >70%. Ex vivo biodistribution was conducted on LnCaP (PSMA(+))and PC3 (PSMA(-)) prostate xenografts implanted on immunodeficient mice at 1, 4, 12 and 24h p.i. PET images were obtained over similar time points. Results Both Zr-89 labeled Mb and Cys-Db PET images showed specific uptake for the LnCaP tumor. Biodistribution experiments on the Mb correlate with the PET image results with tumor uptake peaking at 12h p.i. (~6.2+2.0 %ID/g) with tracer retention at 24h. In contrast, accretion on the PC3 tumor remained constant across all time points with 1.7+0.5%ID/g at 12h p.i. Blocking experiments showed a ~45% decrease in tumor accumulation with 3.4+1.5%ID/g indicative of a receptor-specific uptake mechanism. Ongoing efforts are aimed at quantifying the tissue distribution of Zr-89 Cys-Db, and the results of this analysis will also be presented. Conclusions We demonstrated the potential of Zr-89 Mb and Cys-Db as imaging agents for PSMA(+)prostate cancer. Utilization of these engineered antibody fragments provides rapid tumor accumulation with fast background tissue clearance, thus, affording enhanced tumor-to-background ratios at earlier time points compared to the unmodified antibody. Research Support Geoffrey Beene Cancer Grant (JSL