Euromedim 2006 :1st European Conference on Molecular Imaging Technology

Early Detection of Tumor Masses in Mice by In Vivo Hematoporphyrin mediated Fluorescence Imaging

11 May 2006, 14:00

1h

Palais du Pharo, Marseille

poster • Biomedical perspectives and technical challenges for morpho-functional imaging (multimodality : PET/CT,SPECT/CT,PET/MRI,SPECT/MRI ...) Poster session : Imaging systems, Molecular Imaging

Speaker

Dr Maddalena Autiero (Università degli studi di Napoli "Federico II")

Description

In the last years we have tested hematoporphyrin (HP) dichlorohydrate as an optical contrast agent for the in vivo detection of solid surface tumors on small animals (mice) by Fluorescence Reflectance Imaging (FRI). HP dichlorohydrate was shown to accumulate in tumors, but the volume of the studied tumors was about 50-400 mm3, so that the tumor masses were visible with the naked eye and palpable. Instead, it is crucial in the tumor diagnostic the detection of tumors in their early stage: earlier diagnosis greater the patient survival probability, especially if the tumor is highly invasive. In this work, we apply HP-FRI to image in vivo the HP red fluorescence emission from mouse regions injected with tumor cells of high malignancy degree, in order to study the onset and the growth of the tumor and its early detectability. To this purpose, we improved our previous setup with a high sensitivity, high photometric resolution, monochrome, cooled digital CCD camera. The fluorescence excitation is supplied by a frequency doubled pulsed Nd:YAG laser (532 nm). The cooled digital CCD camera (Hamamatsu ORCA 285 G) records the HP fluorescence radiation (at 630 and 690 nm) filtered by a cut-on long-wavelength pass filter (cut-on wavelength = 600 nm) that rejects the backscattered radiation at 532 nm. About 106 ARO (anaplastic human thyroid carcinoma, highly malignant) cells were implanted subcutaneously in the back of several mice and their growing was monitored about daily through HP-FRI measurements for approximately 10 days starting from the fifth day after the cell injection and 6 h after HP injection. By exploiting the selective HP uptake by the tumor tissues and the high sensitivity of the CCD camera, we have imaged the fluorescence of tumors implanted only five days before the HP-FRI measurements, and, as a consequence, non visible with the naked eye and undetectable to the palpation. HP uptake appears different for healthy and tumor tissues so that the maximum optical contrast tumor-healthy tissue is obtained 24 h after HP administration. HP dichlorohydrate, through it is an aspecific fluorescent tumor marker, is suitable to detect subcutaneous tumor masses with a number of cells of the order of tens of millions (corresponding to a volume of few cube millimiters). Owing to the penetration depth in the tissues of emission red light of fluorophores exogenous (pheophorbide, probably), are detectable also some tumor-free internal organs. The features of this optical imaging system make it suitable for an integration with radionuclide imaging systems. Indeed, we combined it with Medipix2 hybrid pixel detectors (256x256 pixels of 55 micron pitch, 14x14 mm2 sensitive area) with silicon or CdTe pixel detector. A coded mask collimator with hole size of the order of 1-2 pixels would allow for a submillimetric spatial resolution. The resulting multimodal imaging system for small animals aims at reaching high spatial resolution (< 1 mm), short acquisition times, reliability, ease of use, compactness and relatively low cost. By taking planar views of the animal, the system can produce in vivo images of surface tumor masses grown in mice, using 99mTc MIBI as a radiotracer and hematoporphyrin (HP) dichlorohydrate as an exogenous optical fluorophore. Finally, the availability of radionuclide labelled porphyrins makes possible to administer at the same time both the gamma emitting radiotracer and the fluorescent marker, when aiming at a combined radionuclide / fluorescence imaging.