¹⁷⁷Lu-DO3A-HSA-Z _EGFR:1907: Characterization as a potential radiopharmaceutical for radionuclide therapy of EGFR-expressing head and neck carcinomas

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 ⁶⁴Cu or ¹⁷⁷Lu 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 ¹⁷⁷Lu-DO3A-HSA-Z _EGFR:1907 as determined by blocking with nonradioactive Z _EGFR:1907. The internalization of ¹⁷⁷Lu-DO3A-HSA-Z _EGFR:1907 was verified in vitro and found to be significantly higher than that of ¹⁷⁷Lu-labeled Z _EFGR at 2-24 h of incubation. PET and SPECT studies showed good tumor imaging contrasts. The biodistribution of ¹⁷⁷Lu-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. ¹⁷⁷Lu-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.