TY - JOUR
T1 - Three-dimensional histologic validation of high-resolution SPECT of antibody distributions within xenografts
AU - Branderhorst, Woutjan
AU - Blezer, Erwin L. A.
AU - Houtkamp, Mischa
AU - Ramakers, Ruud M.
AU - van den Brakel, Jeroen H.
AU - Witteveen, Henry
AU - van der Have, Frans
AU - Gratama van Andel, Hugo A.
AU - Vastenhouw, Brendan
AU - Wu, Chao
AU - Stigter-van Walsum, Marijke
AU - van Dongen, Guus A. M. S.
AU - Viergever, Max A.
AU - Bleeker, Wim K.
AU - Beekman, Freek J.
PY - 2014
Y1 - 2014
N2 - 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. (111)In-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. 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). (111)In-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. Multipinhole SPECT enables high-resolution visualization and quantification of the heterogeneity of (111)In-zalutumumab concentrations in vivo
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. (111)In-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. 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). (111)In-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. Multipinhole SPECT enables high-resolution visualization and quantification of the heterogeneity of (111)In-zalutumumab concentrations in vivo
U2 - https://doi.org/10.2967/jnumed.113.125401
DO - https://doi.org/10.2967/jnumed.113.125401
M3 - Article
C2 - 24686779
SN - 0161-5505
VL - 55
SP - 830
EP - 837
JO - Journal of nuclear medicine
JF - Journal of nuclear medicine
IS - 5
ER -