title: [64Cu]XYIMSR-06: A dual-motif CAIX ligand for PET imaging of clear cell renal cell carcinoma.
abstract: Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [64Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5% (n=5) and specific activities of 4.1 - 8.9 GBq/μmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h. Biodistribution studies demonstrated a maximum tumor uptake of 19.3% injected dose per gram of radioactivity at 4 h. Tumor-to-blood, -muscle and -kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.3, respectively, at 8 h post-injection. At 24 h a tumor-to-kidney ratio of 7.1 ± 2.5 was achieved. These results indicate pharmacokinetics superior to those of previously reported imaging agents binding to CAIX. [64Cu]XYIMSR-06 is a new low-molecular-weight PET ligand targeting CAIX, which can image localized and metastatic ccRCC.
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: 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: 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: 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: Steven P
authors.initials: SP
authors.lastname: Rowe
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: 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: William D
authors.initials: WD
authors.lastname: Lewis
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hye-Hyun
authors.initials: HH
authors.lastname: Ahn
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Wang
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: 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
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
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry*; D000071231:Carbonic Anhydrase IX / Q000737:chemistry*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000473:pathology; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes / Q000737:chemistry*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D008024:Ligands; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000951:Antigens, Neoplasm; D003301:Copper Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX
keywords: carbonic anhydrase IX; copper-64; molecular imaging; positron emission tomography; renal cell carcinoma