title: Clinical translation of (177)Lu-labeled PSMA-617: Initial experience in prostate cancer patients.
abstract: PSMA-617 is reported to exhibit very high binding affinity towards PSMA receptors, over-expressed on prostate cancer cells and therefore, (177)Lu-labeled PSMA-617 is expected to play a pivotal role in the clinical management of patients suffering from ca prostate. The objective of the present study is to formulate the patient dose of (177)Lu-labeled PSMA-617, pre-clinical studies in animal model and clinical investigation in limited number of prostate cancer patients as well evaluating its potential for theranostic application.
  
  
  
  Patient dose of 7.4 GBq (200 mCi) of (177)Lu-labeled PSMA-617 was prepared by incubating 100 μg of PSMA-617 with (177)LuCl3 at 95 °C for 15 minutes. Radiochemical purity as well as in-vitro stability of the preparation was determined by PC and HPLC methods. The pharmacokinetic behavior and in-vivo distribution of the agent were studied by carrying out biodistribution studies in normal male Wistar rats. Preliminary clinical investigation was performed in 7 patients suffering from prostate cancer.
  
  
  
  The complex was prepared with >98% radiochemical purity under the optimized reaction protocols and the preparation exhibited adequate in-vitro stability. Biodistribution studies revealed no significant uptake in any of the major organ/tissue along with major clearance through renal pathway. Clinical studies showed similar distribution in lesions and physiologic areas of uptake as seen in diagnostic (68)Ga-PSMA-11 PET scans performed earlier.
  
  
  
  Preliminary clinical studies indicated the promising potential of the agent for theranostic applications. However, further investigations in large pool of patients are warranted to establish the theranostic potential of the agent.
authors.affiliation: Radiopharmaceuticals Chemistry Section, Radiochemistry and Isotope Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400 094, India. Electronic address: tdas@barc.gov.in.
authors.forename: Tapas
authors.initials: T
authors.lastname: Das
authors.affiliation: Radiopharmaceuticals Chemistry Section, Radiochemistry and Isotope Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India.
authors.forename: Mohini
authors.initials: M
authors.lastname: Guleria
authors.affiliation: Department of Nuclear Medicine, Jaslok Hospital and Research Centre, Mumbai 400 026, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Parab
authors.affiliation: Department of Nuclear Medicine, Jaslok Hospital and Research Centre, Mumbai 400 026, India.
authors.forename: Chanchala
authors.initials: C
authors.lastname: Kale
authors.affiliation: Department of Nuclear Medicine, Jaslok Hospital and Research Centre, Mumbai 400 026, India.
authors.forename: Hina
authors.initials: H
authors.lastname: Shah
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India.
authors.forename: Haladhar D
authors.initials: HD
authors.lastname: Sarma
authors.affiliation: Department of Nuclear Medicine, Jaslok Hospital and Research Centre, Mumbai 400 026, India.
authors.forename: Vikram R
authors.initials: VR
authors.lastname: Lele
authors.affiliation: Radiopharmaceuticals Chemistry Section, Radiochemistry and Isotope Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400 094, India. Electronic address: sharmila@barc.gov.in.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004151:Dipeptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004355:Drug Stability; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008187:Lutetium / Q000627:therapeutic use*; D008297:Male; D049268:Positron-Emission Tomography; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D011829:Radiation Dosage; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D057170:Translational Research, Biomedical
chemical_list: D004151:Dipeptides; D006573:Heterocyclic Compounds, 1-Ring; C000602389:PSMA-617; D008187:Lutetium; D017430:Prostate-Specific Antigen
keywords: (177)Lu; PSMA-617; Prostate cancer; Targeted radionuclide therapy; Theranostic application