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Background  Patients with squamous cell carcinoma in the head and neck region (HNSCC) offer a diagnostic challenge due to difficulties to detect small tumours and metastases. Imaging methods available are not sufficient, and radio-immunodiagnostics could increase specificity and sensitivity of diagnostics. The objective of this study was to evaluate, for the first time, the  in vivo  properties of the radiolabelled CD44v6-targeting fragment AbD15179 and to assess its utility as a targeting agent for radio-immunodiagnostics of CD44v6-expressing tumours.    Methods  The fully human CD44v6-targeting Fab fragment AbD15179 was labelled with  111 In or  125 I, as models for radionuclides suitable for imaging with SPECT or PET. Species specificity, antigen specificity and internalization properties were first assessed  in vitro. In vivo  specificity and biodistribution were then evaluated in tumour-bearing mice using a dual-tumour and dual-isotope setup.    Results  Both species-specific and antigen-specific binding of the conjugates were demonstrated  in vitro , with no detectable internalization. The  in vivo  studies demonstrated specific tumour binding and favourable tumour targeting properties for both conjugates, albeit with higher tumour uptake, slower tumour dissociation, higher tumour-to-blood ratio and higher CD44v6 sensitivity for the  111 In-labelled fragment. In contrast, the  125 I-Fab demonstrated more favourable tumour-to-organ ratios for liver, spleen and kidneys.    Conclusions  We conclude that AbD15179 efficiently targets CD44v6-expressing squamous cell carcinoma xenografts, and particularly, the  111 In-Fab displayed high and specific tumour uptake. CD44v6 emerges as a suitable target for radio-immunodiagnostics, and a fully human antibody fragment such as AbD15179 can enable further clinical imaging studies.

In vivo characterization of the novel CD44v6-targeting Fab fragment AbD15179 for molecular imaging of squamous cell carcinoma: a dual-isotope study