title: Evaluation of (99m)Tc-probestin SPECT as a novel technique for noninvasive imaging of kidney aminopeptidase N expression.
abstract: Aminopeptidase N (APN; CD13; EC 3.4.11.2) is a zinc-dependent membrane-bound exopeptidase that catalyzes the removal of N-terminal amino acids from peptides. APN is known to be highly expressed on renal cortical proximal tubules. APN expression levels are markedly decreased under the influence of nephrotoxins and in the tumor regions of renal cancers. Thus, molecular imaging of kidney APN expression could provide pathophysiological information about kidneys noninvasively. Probestin is a potent APN inhibitor and binds to APN. Abdominal SPECT imaging was conducted at 1 h postinjection of (99m)Tc-probestin in a group of 12 UPII-SV40T transgenic and wild-type mice. UPII-SV40T mice spontaneously develop urothelial carcinoma in situ and invasive transitional cell carcinoma (TCC) that invade kidneys. Histopathology and immunohistochemistry analysis were used to confirm the presence of tumor and to evaluate APN expression in kidney. Radioactivity in normal tissue regions of renal cortex was clearly visible in SPECT images, whereas tumor regions of renal cortex displayed significantly lower or no radioactivity uptake. Histopathological analysis of kidney sections showed normal morphology for both renal pelvic and cortical regions in wild-type mice and abnormal morphology in some transgenic mice. Proliferating cell nuclear antigen staining confirmed the presence of tumor in those abnormal regions. Immunohistochemical analysis of kidney sections using anti-CD13 antibody showed significantly lower APN expression in tumor regions compared to normal regions. Results obtained in this study demonstrate the potential use of (99m)Tc-probestin SPECT as a novel technique for noninvasive imaging of kidney APN expression.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, ‡Center for Cancer Prevention and Drug Development, Hematology/Oncology Section, Department of Medicine, §PCS Oklahoma Cancer Center, and ∥Nephrology Section, Department of Medicine, College of Medicine, The University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73117, United States.
authors.forename: Gopal
authors.initials: G
authors.lastname: Pathuri
authors.forename: Venkateshwar
authors.initials: V
authors.lastname: Madka
authors.forename: Andria F
authors.initials: AF
authors.lastname: Hedrick
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Lightfoot
authors.forename: Vibhudutta
authors.initials: V
authors.lastname: Awasthi
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Cowley
authors.forename: Chinthalapally V
authors.initials: CV
authors.lastname: Rao
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Gali
mesh_terms: D000409:Alanine / Q000737:chemistry; D000818:Animals; D018826:CD13 Antigens / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D007150:Immunohistochemistry; D007668:Kidney / Q000000981:diagnostic imaging*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011868:Radioisotopes / Q000737:chemistry; D013667:Technetium / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D019459:Urothelium / Q000000981:diagnostic imaging*
chemical_list: D009842:Oligopeptides; D010455:Peptides; D011868:Radioisotopes; C063432:probestin; D013667:Technetium; D010447:Peptide Hydrolases; D018826:CD13 Antigens; D000409:Alanine