Abstract 58: Comparative determination of compound delivery to orthotopic and subcutaneous tumors by non-invasive imaging
Authors: Shi Jing , Mohajerani Pouyan , Morscher Stefan , Driessen Wouter , Burton Neal , Razansky Daniel , Ntziachristos Vasilis 
Published: August 2012

Abstract
Cancer is fundamentally a disease of aberrant tissue growth and determining accurate progression in malignancies is of significant importance for the understanding of the heterogeneous growth patterns, and irregular nature of malignant tumors. Here we used two different imaging modalities to detect tumor progression, and highlight the inherent challenges with accurate determination of growth characteristics. The main focus in this study was to examine the differences in compound deposition and uptake into orthotopically and subcutaneously implanted tumors. Several perfusion studies with Indocyanine green (ICG) were performed and compound kinetics and distribution within the tumors were determined by MSOT and FMT-XCT. Multi-Spectral Optoacoustic Tomography (MSOT) is a powerful novel imaging modality that decomposes the spectral responses of endogenous and exogenous chromophores in vivo, with high resolution and at depths ranging from several millimeters to centimeters. Therefore, it can simultaneously detect and separate the signal of endogenous chromophores such as (oxy)hemoglobin and extrinsically administered photo-absorbing agents such as ICG and nanoparticles. FMT-XCT is an imaging system that integrates X-ray computed tomography (XCT) and fluorescence molecular tomography (FMT), enabling quantitative, volumetric detection of fluorescent agents with co-registration of anatomical features. For the subcutaneous model, HT29 human colon adenocarcinoma cells (∼106) were injected subcutaneously in the hind limb of CD1 nude mice (Charles River Laboratories, Germany). For the syngeneic, orthotopic model, Balb/c mice (Charles River Laboratories, Germany) were injected with 4T1 mouse mammary tumor cells (∼0.5x106) into the mammary fat pad. With MSOT imaging after ICG injection (50µg) we were able to show that the vascular perfusion of subcutaneous tumors was limited to the outer edges of the tumor, caused by necrosis within these tumors. The orthotopically implanted tumors were much better perfused and compound delivery throughout the entire tumor was achieved. A major advantage of MSOT imaging compared to FMT-XCT is that contrast agents and oxygenated vs. deoxygenated hemoglobin can be visualized non-invasively at the tumor site simultaneously with high spatial resolution, in real time, and throughout the entire period of tumor growth. Using FMT-XCT we were able to assess further information about the three-dimensional distribution of ICG within the entire animal. These findings show that the heterogeneity of tumors can be visualized non-invasively using MSOT and FMT-XCT. MSOT has the added advantage that endogenous chromophores such as hemoglobin can be resolved simultaneously. These imaging strategies are of critical importance to monitor tumor progression in order to evaluate appropriate treatment regimens and/ or stratify tumors based on oxygenation status.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 58. doi:1538-7445.AM2012-58