Radiopharmacology of an Anti-CEA Monoclonal Antibody-l-RNA / l-DNA Duplex Pretargeting System
Radiopharmacology of an Anti-CEA Monoclonal Antibody-l-RNA / l-DNA Duplex Pretargeting System
Bergmann, R.; Schlesinger, J.; Koezle, I.; Förster, C.; Klussmann, S.; Vonhoff, S.; Pietzsch, H.-J.; Pietzsch, J.; Wüst, F.; Behrsin, O.; Micheel, B.; Steinbach, J.
Ziel/Aim:
This current study is aimed at demonstrating of the applicability of l‑oligonucleotides as a novel recognition system for pretargeting using a radiolabeled 17mer l‑DNA and complementary l‑RNA bound to microspheres and an antibody as targeting vector.
Methodik/Methods:
Small animal PET, biodistribution and metabolite studies of Ga-68 and Y-86-labeled L-DNA were carried out in rats and mice. Hybridization in vivo was demonstrated through cl‑RNA-modified microspheres trapped in the lungs and injection of complementary Ga-68-labeled 17mer l‑DNA. Tumor accumulation and pharmocokinetics in the human colon carcinoma models LS174T (n=10) and LoVo (n=2) tumors on NMRI nu/nu mice were evaluated with a 17mer cl‑RNA modified anti CEACAM5 (CEA) antibody aCEA(IG1)D11-DG2 and Ga-68-L-DNA.
Ergebnisse/Results:
The Ga-68- and Y-86-labeled L-DNAs showed typical biodistributions pattern of hydrophylic compounds with fast renal elimination and displayed high metabolic stability in vivo. cl‑RNA-microspheres trapped in the lungs could be visualized (SUV=0.51), i.e. 1.5%ID of the Ga-68-labeled 17mer l‑DNA were hybridized with the cl‑RNA on the microspheres. The LS174T and LoVo tumors were clearly visible with SUVs (median, 25%; 75% percentile) of 0.20 (0.19; 0.31) and 0.18 (0.16; 0.19), respectively. The averaged tumor/muscle ratio was 5.4±0.4 by administering the DG2 immunoconjugate first and injection of radiolabeled L-DNA after a 24 h delay.
Schlussfolgerungen/Conclusions:
Preliminary results demonstrate that the recognition system has promising properties for pretargeting in vivo to improve molecular imaging and therapy of solid tumors.
Involved research facilities
- PET-Center
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Lecture (Conference)
52. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin (DGN), 26.-29.03.2014, Hannover, Deutschland -
Abstract in refereed journal
Nuklearmedizin 53(2014), A49
ISSN: 0029-5566
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