Tumor hypoxia plays a major role in radio- and
chemotherapy resistance in solid
tumors.
Carbonic Anhydrase IX (CAIX) is an endogenous
hypoxia-related
protein, which is associated with poor patient outcome. The quantitative assessment of CAIX expression of
tumors may steer
cancer treatment by predicting
therapy response or patient selection for antihypoxia or CAIX-targeted treatment. Recently, the single-photon emission computerized tomography (SPECT) tracer [111In]In-
DTPA-
girentuximab-F(ab')2 was developed and validated for targeting CAIX. The aim of this study was to optimize quantitative microSPECT/CT of CAIX expression in vivo in head and neck
tumor models. Athymic mice with subcutaneous SCCNij153 and SCCNij202
head and neck squamous cell carcinoma xenografts were injected with [111In]In-
DTPA-
girentuximab-F(ab')2. First, the
protein dose, timing, and image acquisition settings were optimized. Tracer uptake was determined by quantitative SPECT, ex vivo radioactivity counting, and by autoradiography of
tumor sections. The same
tumor sections were immunohistochemically stained for CAIX expression and
hypoxia. Highest
tumor-normal-tissue contrast was obtained at 24 h after injection of the tracer. A
protein dose of 10 μg resulted in the highest
tumor-to-muscle ratio at 24 h p.i. Ex vivo biodistribution studies showed a
tumor uptake of 3.0 ± 0.6%ID/g and a
tumor-to-muscle ratio of 8.7 ± 1.4 (SCCNij153). Quantitative analysis of the SPECT images enabled us to distinguish CAIX
antigen blocked from nonblocked
tumors, fractions positive for CAIX expression: 0.22 ± 0.02 versus 0.08 ± 0.01 ( p < 0.01). Immunohistochemical, autoradiographic, and microSPECT/CT analyses showed a distinct intratumoral spatial correlation between localization of the radiotracer and CAIX expression. Here, we demonstrate that [111In]In-
DTPA-
girentuximab-F(ab')2 specifically targets CAIX-expressing cells in
head and neck cancer xenografts. SPECT imaging with
indium-labeled girentuximab-F(ab')2 allows quantitative assessment of the fraction of CAIX positive tissue in
head and neck cancer xenografts. These results indicate that [111In]In-
DTPA-
girentuximab-F(ab')2 is a promising tracer to image
hypoxia-related CAIX expression.