title: 99mTc-labeling and evaluation of a HYNIC modified small-molecular inhibitor of prostate-specific membrane antigen.
abstract: BACKGROUND
  Prostate-specific membrane antigen (PSMA) is a well-established target in the development of radiopharmaceuticals for the diagnosis and therapy of prostate cancer (PCa). In this study, we evaluated a novel99mTc-labeled small molecular inhibitor of PSMA.
  
  
  METHODS
  This new small-molecular inhibitor of PSMA, 6-hydrazinonicotinate-Aminocaproic acid-Lysine-Urea-Glutamate (HYNIC-ALUG) was radiolabeled by99mTc and was evaluated both in vitro and in vivo using PCa models (PC-3 and LNCaP). Radiation dosimetry was assessed in mice.
  
  
  RESULTS
  99mTc-HYNIC-ALUG showed excellent stability in different media. A cell assay preliminarily displayed its specificity for PSMA. The inhibitor showed good pharmacokinetics making it suitable for in vivo imaging. PC-3-derived tumors showed no obvious radioactive uptake; however, the LNCaP-derived tumors showed very high radioactive uptake which was significantly decreased by the selective PSMA inhibitor 2-PMPA. Biodistribution in LNCaP xenografts showed an optimum tumor-to-blood ratio of 24.23±3.54 at 2h. Tumor uptake was also decreased in the inhibition experiment with 2-PMPA (19.45±2.14%ID/g versus 1.42±0.15%ID/g at 2h). The effective dose of the99mTc-HYNIC-ALUG was 8.4E-04mSv/MBq.
  
  
  CONCLUSIONS
  A new99mTc-labeled PSMA inhibitor with specific accumulation in PSMA-positive tumors and low background in other organs was synthesized. The radiopharmaceutical also showed very low radiation dosimetry. This agent may significantly improve the diagnosis, staging, and subsequent monitoring of therapeutic effects in PCa patients.
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China; Shanghai Proton and Heavy Ion Center, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China; Shanghai Proton and Heavy Ion Center, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China; Shanghai Proton and Heavy Ion Center, Fudan University Shanghai Cancer Center, Shanghai 200032, China. Electronic address: husilong0071@163.com.
authors.forename: Silong
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China.
authors.forename: Simin
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Bao
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ma
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China; Shanghai Proton and Heavy Ion Center, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China; Shanghai Proton and Heavy Ion Center, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000954:Antigens, Surface; D001692:Biological Transport; D045744:Cell Line, Tumor; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D000431:Ethanol / Q000737:chemistry; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors*; D006834:Hydrazines / Q000737:chemistry*; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D009539:Nicotinic Acids / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D013667:Technetium; D014018:Tissue Distribution; D014508:Urea / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D014867:Water / Q000737:chemistry
chemical_list: C120392:6-hydrazinopyridine-3-carboxylic acid; D000954:Antigens, Surface; D004791:Enzyme Inhibitors; D006834:Hydrazines; D009539:Nicotinic Acids; D014867:Water; D000431:Ethanol; D013667:Technetium; D014508:Urea; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: (99m)Tc-radiolabeled agents; Nano-SPECT imaging; PSMA inhibitor; Prostate cancer; Radiation dosimetry