The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule

Abstract

Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The 111In-labelled DOTA-conjugated ZEGFR:2377 Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-ZEGFR:2377. DOTA-ZEGFR:2377 was labelled with 57Co (T1/2 = 271.8 d), 55Co (T1/2 = 17.5 h), and, for comparison, with the positron-emitting radionuclide 68Ga (T1/2 = 67.6 min) with preserved specificity of binding to EGFR-expressing A431 cells. The long-lived cobalt radioisotope 57Co was used in animal studies. Both 57Co-DOTA-ZEGFR:2377 and 68Ga-DOTA-ZEGFR:2377 demonstrated EGFR-specific accumulation in A431 xenografts and EGFR-expressing tissues in mice. Tumour-to-organ ratios for the radiocobalt-labelled DOTA-ZEGFR:2377 were significantly higher than for the gallium-labelled counterpart already at 3 h after injection. Importantly, 57Co-DOTA-ZEGFR:2377 demonstrated a tumour-to-liver ratio of 3, which is 7-fold higher than the tumour-to-liver ratio for 68Ga-DOTA-ZEGFR:2377. The results of this study suggest that the positron-emitting cobalt isotope 55Co would be an optimal label for DOTA-ZEGFR:2377 and further development should concentrate on this radionuclide as a label.

Same-Day Imaging Using Small Proteins: Clinical Experience and Translational Prospects in Oncology

“…Labeling of DOTA-ZEGFR:2377 with 68 Ga and 57/55 Co was assessed. Evaluation of conjugates in A431 xenografts demonstrated that labeling of ZEGFR:2377 with 57/55 Co provided significantly higher tumor-to-organ ratios than did labeling with 68 Ga (43). Importantly, a tumor-to-liver ratio of 3.1 6 0.5 (3 h after injection) was obtained (Fig.…”

“…Jiang et al reported the potential use of a 7C knottin peptide as a SPECT probe for imaging of integrin a v b 3 -positive (28)(29)(30)(31)(32)43) and with permission of (28,30,31).) K 5 kidney; L 5 liver.…”

PET radiometals for antibody labeling

“…67,72 More recently, this radionuclide has shown promise for labeling affibodies. The DOTA-Z2395-C affibody was efficiently and stably labeled with 57 Co. 68 The intercellular retention of radiocobaltlabeled DOTA-Z2395-C was comparable to the retention of its 111 In-labeled counterpart in vitro. In vivo, the radiocobalt label provided better tumor-to-organ ratios than the radionuclide 111 In.…”

“…64 55 Co can be produced via either the 58 Ni(p,α) 55 Co or the 54 Fe(d,n) 55 Co nuclear reactions at low energy biomedical cyclotrons and possesses a half-life permissive of centralized production and distribution. 64,65 After irradiation, the produced 55 Co can be separated from the target material using an extraction resin functionalized with N,N,N′, N′-tetrakis-2-ethylhexyldiglycolamide, or branched DGA (Eichrom, Illinois). 64 As with many of the radiometals discussed herein, radiocobalt can be efficiently coordinated using common hard donor chelators such as such as DOTA, HBED, TETA, and NOTA, 66-68 but to date, strategies for the labeling of mAbs or proteins with 55 Co have not been well established.…”

“…This step is essential to radiotracers' "smart" design and ensures that the time course of the radioactivity matches that of the mAb. 7 Typically, due to prolonged circulation half-lives, antibodies' accumulation in tumors tends to peak days after injection, which makes necessary the use of long half-life isotopes (eg, 89 Zr, 64 Cu, and 86 Y) instead of more traditional choices such as 11 C, 18 F, or 68 Ga. In instances where the conventional isotopes do not suit the desired application, other interesting radionuclides have been investigated which offer more appropriate chemical or decay properties.…”