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 potential
radiopharmaceutical for radionuclide therapy of EGFR-expressing head and neck

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-X
Program, Canary Center at Stanford for Cancer Early Detection, Stanford
University, 1201 Welch Road, Lucas Expansion, P095, Stanford, CA, 94305, USA.

Epidermal growth factor receptor 1 (EGFR) is an attractive target for
radionuclide therapy of head and neck carcinomas. Affibody molecules against EGFR
(Z(EGFR)) show excellent tumor localizations in imaging studies. However, one
major drawback is that radiometal-labeled Affibody molecules display extremely
high uptakes in the radiosensitive kidneys which may impact their use as
radiotherapeutic agents. The purpose of this study is to further explore whether
radiometal-labeled human serum albumin (HSA)-Z(EFGR) bioconjugates display
desirable 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-specifically
conjugated with HSA. The resulting bioconjugate
1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A)-HSA-Z(EGFR:1907) was
then radiolabeled with either (64)Cu or (177)Lu and subjected to in vitro cell
uptake and internalization studies using the human oral squamous carcinoma cell
line SAS. Positron emission tomography (PET), single photon emission computed
tomography (SPECT), and biodistribution studies were conducted using
SAS-tumor-bearing mice. Cell studies revealed a high (8.43 ± 0.55 % at 4 h) and
specific (0.95 ± 0.09 % at 4 h) uptake of (177)Lu-DO3A-HSA-Z(EGFR:1907) as
determined 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 significantly
higher than that of (177)Lu-labeled Z(EFGR) at 2-24 h of incubation. PET and
SPECT studies showed good tumor imaging contrasts. The biodistribution of
(177)Lu-DO3A-HSA-Z(EGFR:1907) in SAS-tumor-bearing mice displayed high tumor
uptake (5.1 ± 0.44 % ID/g) and liver uptake (31.5 ± 7.66 % ID/g) and moderate
kidney 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 a
potential radiopharmaceutical for radionuclide therapy of EGFR-expressing head
and neck carcinomas.

PMID: 22418921 [PubMed - as supplied by publisher]