2 research outputs found
Multimodality Imaging of Breast Cancer Experimental Lung Metastasis with Bioluminescence and a Monoclonal Antibody Dual-Labeled with <sup>89</sup>Zr and IRDye 800CW
Metastatic breast cancer is incurable. The goal of this
study was
to develop a positron emission tomography (PET)/near-infrared fluorescent
(NIRF) probe for imaging CD105 expression in breast cancer experimental
lung metastasis. TRC105, a chimeric anti-CD105 antibody, was dual-labeled
with a NIRF dye (IRDye 800CW) and <sup>89</sup>Zr to yield <sup>89</sup>Zr-Df-TRC105-800CW. Luciferase-transfected 4T1 murine breast cancer
cells were injected intravenously into female mice to establish the
tumor model. Bioluminescence imaging (BLI) was carried out to noninvasively
monitor the lung tumor burden. PET imaging revealed that 4T1 lung
tumor uptake of <sup>89</sup>Zr-Df-TRC105-800CW was 8.7 ± 1.4,
10.9 ± 0.5, and 9.7 ± 1.1% ID/g at 4, 24, and 48 h postinjection
(<i>n</i> = 4), with excellent tumor contrast. Biodistribution
studies, blocking, control studies with <sup>89</sup>Zr-Df-cetuximab-800CW,
ex vivo BLI/PET/NIRF imaging, and histology all confirmed CD105 specificity
of the tracer. Broad clinical potential of TRC105-based agents was
shown in many tumor types, which also enabled early detection of small
metastasis and intraoperative guidance for tumor removal
Exploiting the Metal-Chelating Properties of the Drug Cargo for <i>In Vivo</i> Positron Emission Tomography Imaging of Liposomal Nanomedicines
The
clinical value of current and future nanomedicines can be improved
by introducing patient selection strategies based on noninvasive sensitive
whole-body imaging techniques such as positron emission tomography
(PET). Thus, a broad method to radiolabel and track preformed nanomedicines
such as liposomal drugs with PET radionuclides will have a wide impact
in nanomedicine. Here, we introduce a simple and efficient PET radiolabeling
method that exploits the metal-chelating properties of certain drugs
(<i>e.g.</i>, bisphosphonates such as alendronate and anthracyclines
such as doxorubicin) and widely used ionophores to achieve excellent
radiolabeling yields, purities, and stabilities with <sup>89</sup>Zr, <sup>52</sup>Mn, and <sup>64</sup>Cu, and without the requirement
of modification of the nanomedicine components. In a model of metastatic
breast cancer, we demonstrate that this technique allows quantification
of the biodistribution of a radiolabeled stealth liposomal nanomedicine
containing alendronate that shows high uptake in primary tumors and
metastatic organs. The versatility, efficiency, simplicity, and GMP
compatibility of this method may enable submicrodosing imaging studies
of liposomal nanomedicines containing chelating drugs in humans and
may have clinical impact by facilitating the introduction of image-guided
therapeutic strategies in current and future nanomedicine clinical
studies