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.
Highlights
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
We have shown that the anti-epidermal growth factor receptor (EGFR) 111In-DOTA-ZEGFR:2377 Affibody molecule can visualize EGFR expression in murine xenografts[15]
The molecular mass of DOTA-ZEGFR:2377 was determined by mass spectrometric analysis and showed a good agreement with the theoretical value (Supplementary Fig. S2)
Summary
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. Radionuclide molecular imaging is a potential method for in vivo measurement of EGFR expression in malignant tumours. A clinical study has demonstrated that it is possible to find an injected anti-EGFR antibody dose capable of providing a partial saturation of EGFR in the liver without target saturation in tumours enabling visualization of EGFR-expressing malignancies using radiolabelled antibodies[11]. In vivo molecular imaging using radiolabelled Affibody molecules has been demonstrated in preclinical studies for several cancer-related molecular targets, e.g. HER2, EGFR, HER3, and IGF-1R. We have shown that the anti-EGFR 111In-DOTA-ZEGFR:2377 Affibody molecule can visualize EGFR expression in murine xenografts[15]. Our studies showed that injection of 30–50 μg 111In-DOTA-ZEGFR:2377 provides partial saturation of EGFR in normal tissues without saturating the target in tumours[15]. The tumour-to-blood ratios at optimal dosage were 7.0 ± 0.5 and 14 ± 4, at 4 and 24 h after injection, respectively
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