title: Imaging of carbonic anhydrase IX with an 111In-labeled dual-motif inhibitor.
abstract: We developed a new scaffold for radionuclide-based imaging and therapy of clear cell renal cell carcinoma (ccRCC) targeting carbonic anhydrase IX (CAIX). Compound XYIMSR-01, a DOTA-conjugated, bivalent, low-molecular-weight ligand, has two moieties that target two separate sites on CAIX, imparting high affinity. We synthesized [111In]XYIMSR-01 in 73.8-75.8% (n = 3) yield with specific radioactivities ranging from 118 - 1,021 GBq/μmol (3,200-27,600 Ci/mmol). Single photon emission computed tomography of [111In]XYIMSR-01 in immunocompromised mice bearing CAIX-expressing SK-RC-52 tumors revealed radiotracer uptake in tumor as early as 1 h post-injection. Biodistribution studies demonstrated 26% injected dose per gram of radioactivity within tumor at 1 h. Tumor-to-blood, muscle and kidney ratios were 178.1 ± 145.4, 68.4 ± 29.0 and 1.7 ± 1.2, respectively, at 24 h post-injection. Retention of radioactivity was exclusively observed in tumors by 48 h, the latest time point evaluated. The dual targeting strategy to engage CAIX enabled specific detection of ccRCC in this xenograft model, with pharmacokinetics surpassing those of previously described radionuclide-based probes against CAIX.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Il
authors.initials: I
authors.lastname: Minn
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Rowe
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Sangeeta Ray
authors.initials: SR
authors.lastname: Banerjee
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gorin
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Brummet
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hye Soo
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Soo Min
authors.initials: SM
authors.lastname: Koo
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Polina
authors.initials: P
authors.lastname: Sysa-Shah
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Ronnie C
authors.initials: RC
authors.lastname: Mease
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Mohamad E
authors.initials: ME
authors.lastname: Allaf
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000737:chemistry*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000473:pathology; D002469:Cell Separation; D004791:Enzyme Inhibitors / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D007205:Indium Radioisotopes / Q000737:chemistry*; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology; D008024:Ligands; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008856:Microscopy, Fluorescence / Q000379:methods*; D008970:Molecular Weight; D009368:Neoplasm Transplantation; D019275:Radiopharmaceuticals / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000951:Antigens, Neoplasm; D004791:Enzyme Inhibitors; D007205:Indium Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D016650:Fluorescein-5-isothiocyanate
keywords: CAIX; indium-111; molecular imaging; renal cell carcinoma; single photon emission computed tomography