In vivo localization of 90Y and 177Lu radioimmunoconjugates using Cerenkov luminescence imaging in a disseminated murine leukemia model.

Publication Type:

Journal Article

Source:

Cancer research, Volume 74, Issue 20, p.5846-54 (2014)

Keywords:

Animals, Biologics Production Core Facility, Cell Line, Tumor, Comparative Medicine Core Facility, Experimental Histopathology Core Facility, Female, Flow Cytometry Core Facility, Genomics Core Facility, Immune Monitoring Core Facility, Immunoconjugates, LEUKEMIA, Luminescent Measurements, Lutetium, MICE, Phantoms, Imaging, Proteomics Core Facility, Radiopharmaceuticals, Scientific Imaging Core Facility, Shared Resources, Spleen, TISSUE DISTRIBUTION, Yttrium Radioisotopes

Abstract:

Cerenkov radiation generated by positron-emitting radionuclides can be exploited for a molecular imaging technique known as Cerenkov luminescence imaging (CLI). Data have been limited, however, on the use of medium- to high-energy β-emitting radionuclides of interest for cancer imaging and treatment. We assessed the use of CLI as an adjunct to determine localization of radioimmunoconjugates to hematolymphoid tissues. Radiolabeled (177)Lu- or (90)Y-anti-CD45 antibody (Ab; DOTA-30F11) was administered by tail vein injection to athymic mice bearing disseminated murine myeloid leukemia, with CLI images acquired at times afterward. Gamma counting of individual organs showed preferential uptake in CD45(+) tissues with significant retention of radiolabeled Ab in sites of leukemia (spleen and bone marrow). This result was confirmed in CLI images with 1.35 × 10(5) ± 2.2 × 10(4) p/s/cm(2)/sr and 3.45 × 10(3) ± 7.0 × 10(2) p/s/cm(2)/sr for (90)Y-DOTA-30F11 and (177)Lu-DOTA-30F11, respectively, compared with undetectable signal for both radionuclides using the nonbinding control Ab. Results showed that CLI allows for in vivo visualization of localized β-emissions. Pixel intensity variability resulted from differences in absorbed doses of the associated energies of the β-emitting radionuclide. Overall, our findings offer a preclinical proof of concept for the use of CLI techniques in tandem with currently available clinical diagnostic tools.