RT Journal Article SR Electronic T1 Three-Dimensional Histologic Validation of High-Resolution SPECT of Antibody Distributions Within Xenografts JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 830 OP 837 DO 10.2967/jnumed.113.125401 VO 55 IS 5 A1 Woutjan Branderhorst A1 Erwin L.A. Blezer A1 Mischa Houtkamp A1 Ruud M. Ramakers A1 Jeroen H. van den Brakel A1 Henry Witteveen A1 Frans van der Have A1 Hugo A. Gratama van Andel A1 Brendan Vastenhouw A1 Chao Wu A1 Marijke Stigter-van Walsum A1 Guus A.M.S. van Dongen A1 Max A. Viergever A1 Wim K. Bleeker A1 Freek J. Beekman YR 2014 UL http://jnm.snmjournals.org/content/55/5/830.abstract AB Longitudinal imaging of intratumoral distributions of antibodies in vivo in mouse cancer models is of great importance for developing cancer therapies. In this study, multipinhole SPECT with sub–half-millimeter resolution was tested for exploring intratumoral distributions of radiolabeled antibodies directed toward the epidermal growth factor receptor (EGFr) and compared with full 3-dimensional target expression assessed by immunohistochemistry. Methods: 111In-labeled zalutumumab, a human monoclonal human EGFr-targeting antibody, was administered at a nonsaturating dose to 3 mice with xenografted A431 tumors exhibiting high EGFr expression. Total-body and focused in vivo tumor SPECT was performed at 0 and 48 h after injection and compared both visually and quantitatively with full 3-dimensional immunohistochemical staining for EGFr target expression. Results: SPECT at 48 h after injection showed that activity was predominantly concentrated in the tumor (10.5% ± 1.3% of the total-body activity; average concentration, 30.1% ± 4.6% of the injected dose per cubic centimeter). 111In-labeled EGFr-targeting antibodies were distributed heterogeneously throughout the tumor. Some hot spots were observed near the tumor rim. Immunohistochemistry indicated that the antibody distributions obtained by SPECT were morphologically similar to those obtained for ex vivo EGFr target expression. Regions showing low SPECT activity were necrotic or virtually negative for EGFr target expression. A good correlation (r = 0.86, P < 0.0001) was found between the percentage of regions showing low activity on SPECT and the percentage of necrotic tissue on immunohistochemistry. Conclusion: Multipinhole SPECT enables high-resolution visualization and quantification of the heterogeneity of 111In-zalutumumab concentrations in vivo.