RT Journal Article
SR Electronic
T1 Identification of the optimal Cu-64 bifunctional chelator for radioimmunodetection of neuroblastoma
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 375
OP 375
VO 50
IS supplement 2
A1 Dearling, Jason
A1 Voss, Stephan
A1 Dunning, Patricia
A1 Snay, Erin
A1 Fahey, Frederick
A1 Meares, Claude
A1 Treves, Ted
A1 Smith, Suzanne
A1 Packard, Alan
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/375.abstract
AB 375 Objectives The biodistribution of the anti-GD2 antibody ch14.18 labeled with Cu-64 using 5 bifunctional chelators (BFCs) was measured to determine which provided optimal combination of tumor uptake and clearance from non-target tissues. Methods Five BFCs (pba-NOTA, SarAr, BAT-6, DOTA, and pba-DOTA) were conjugated to ch14.18 and labeled with 64Cu. The radioimmunoconjugates (RIC) (50 μg, 100-250 μCi) were injected into mice (n = 3-5) bearing M21 tumors. MicroPET images were obtained at 1, 24 and 48 h, and biodistribution was measured at 48 h. Results All RICs localized to the tumor, with absolute uptake related to tumor size. Significant differences between the RICs (ANOVA, Bonferroni, P < 0.05) were observed in liver, spleen and kidney, with uptake of the SarAr RIC being higher and pba-NOTA being lower, without a decrease in tumor uptake. For example, at 48 h p.i. the tumor to tissue ratios with pba-NOTA were: liver 3.3:1; kidney 3.1:1, whereas for SarAr the ratios were: liver 2.8:1; kidney 2.3:1. Conclusions The differences in uptake and clearance by the non-target tissues are surprising, given that Cu-NOTA is less stable than Cu-SarAr. The data suggest that the SarAr BFC is providing more accurate information about the biodistribution of the RIC. Cu-64 lost from the less stable complexes is excreted from non-target tissues. Selection of an optimal bifunctional chelator will aid in the development of an improved agent for the detection of neuroblastoma. Research Support National Institutes of Health Grants 5K08CA093554 and 5R01CA094338.