albumin - publications
Predict more albumin - ligand interactions now!
1. J Biol Inorg Chem. 2012 Mar 16. [Epub ahead of print](177)Lu-DO3A-HSA-Z (EGFR:1907): characterization as a potentialradiopharmaceutical for radionuclide therapy of EGFR-expressing head and neckcarcinomas.Hoppmann S, Qi S, Miao Z, Liu H, Jiang H, Cutler CS, Bao A, Cheng Z.Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-XProgram, Canary Center at Stanford for Cancer Early Detection, StanfordUniversity, 1201 Welch Road, Lucas Expansion, P095, Stanford, CA, 94305, USA.Epidermal growth factor receptor 1 (EGFR) is an attractive target forradionuclide therapy of head and neck carcinomas. Affibody molecules against EGFR(Z(EGFR)) show excellent tumor localizations in imaging studies. However, onemajor drawback is that radiometal-labeled Affibody molecules display extremelyhigh uptakes in the radiosensitive kidneys which may impact their use asradiotherapeutic agents. The purpose of this study is to further explore whether radiometal-labeled human serum albumin (HSA)-Z(EFGR) bioconjugates displaydesirable profiles for the use in radionuclide therapy of EGFR-positive head and neck carcinomas. The Z(EFGR) analog, Ac-Cys-Z(EGFR:1907), was site-specificallyconjugated with HSA. The resulting bioconjugate1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A)-HSA-Z(EGFR:1907) wasthen radiolabeled with either (64)Cu or (177)Lu and subjected to in vitro celluptake and internalization studies using the human oral squamous carcinoma cellline SAS. Positron emission tomography (PET), single photon emission computedtomography (SPECT), and biodistribution studies were conducted usingSAS-tumor-bearing mice. Cell studies revealed a high (8.43 ± 0.55 % at 4 h) andspecific (0.95 ± 0.09 % at 4 h) uptake of (177)Lu-DO3A-HSA-Z(EGFR:1907) asdetermined by blocking with nonradioactive Z(EGFR:1907). The internalization of(177)Lu-DO3A-HSA-Z(EGFR:1907) was verified in vitro and found to be significantlyhigher than that of (177)Lu-labeled Z(EFGR) at 2-24 h of incubation. PET andSPECT studies showed good tumor imaging contrasts. The biodistribution of(177)Lu-DO3A-HSA-Z(EGFR:1907) in SAS-tumor-bearing mice displayed high tumoruptake (5.1 ± 0.44 % ID/g) and liver uptake (31.5 ± 7.66 % ID/g) and moderatekidney uptake (8.5 ± 1.08 % ID/g) at 72 h after injection.(177)Lu-DO3A-HSA-Z(EGFR:1907) shows promising in vivo profiles and may be apotential radiopharmaceutical for radionuclide therapy of EGFR-expressing headand neck carcinomas.PMID: 22418921 [PubMed - as supplied by publisher]