title: In vivo localization of ⁹⁰Y and ¹⁷⁷Lu radioimmunoconjugates using Cerenkov luminescence imaging in a disseminated murine leukemia model.
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.
authors.affiliation: Radiation Oncology, University of Washington, Seattle, Washington.
authors.forename: Ethan R
authors.initials: ER
authors.lastname: Balkin
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Aimee
authors.initials: A
authors.lastname: Kenoyer
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Hematology Division, University of Washington, Seattle, Washington.
authors.forename: Johnnie J
authors.initials: JJ
authors.lastname: Orozco
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hernandez
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Medical Oncology, University of Washington, Seattle, Washington.
authors.forename: Mazyar
authors.initials: M
authors.lastname: Shadman
authors.affiliation: Pacific Northwest National Laboratory, Richland, Washington.
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Fisher
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Medical Oncology, University of Washington, Seattle, Washington.
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Green
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hylarides
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Medical Oncology, University of Washington, Seattle, Washington.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.affiliation: Radiation Oncology, University of Washington, Seattle, Washington.
authors.forename: D Scott
authors.initials: DS
authors.lastname: Wilbur
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Medical Oncology, University of Washington, Seattle, Washington. jpagel@fhcrc.org.
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D018796:Immunoconjugates; D007938:Leukemia / Q000000981:diagnostic imaging*; D008163:Luminescent Measurements; D008187:Lutetium; D051379:Mice; D019047:Phantoms, Imaging; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics
chemical_list: D018796:Immunoconjugates; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D008187:Lutetium