title: Application of (99m)Technetium-HYNIC(tricine/TPPTS)-Aca-Bombesin(7-14) SPECT/CT in prostate cancer patients: a first-in-man study.
abstract: BACKGROUND
  The peptide bombesin (BBN) and its derivatives exhibit high binding affinity for the gastrin-releasing peptide receptor (GRPR), which is highly expressed in prostate cancer. We used the BBN-based radiopharmaceutical (99m)Technetium-HYNIC(tricine/TPPTS)-Aca-Bombesin(7-14) ((99m)Tc-HABBN) to perform a first-in-man clinical pilot study to evaluate the feasibility of (99m)Tc-HABBN SPECT/CT for detection of prostate cancer in patients.
  
  
  METHODS
  Eight patients with biopsy-proven prostate cancer who were scheduled for either radical prostatectomy or external beam radiotherapy underwent (99m)Tc-HABBN scintigraphy and SPECT/CT prior to treatment. Serial blood samples were taken to assess blood radioactivity and to determine in vivo metabolic stability. Clinical parameters were measured and reported side effects, if present, were recorded. Prostate cancer specimens of all patients were immunohistochemically stained for GRPR.
  
  
  RESULTS
  (99m)Tc-HABBN was synthesized with high radiochemical yield, purity and specific activity. There were no significant changes in clinical parameters, and there were no adverse or subjective side effects. Low metabolic stability was observed, as less than 20% of (99m)Tc-HABBN was intact after 30 min. Immunohistochemical staining for GRPR was observed in the prostate cancer specimens in all patients. (99m)Tc-HABBN scintigraphy and SPECT/CT did not detect prostate cancer in patients with proven disease.
  
  
  CONCLUSIONS
  (99m)Tc-HABBN SPECT/CT for visualization of prostate cancer is safe but hampered by an unexpected low in vivo metabolic stability in man. The difference between the excellent in vitro stability of (99m)Tc-HABBN in human serum samples determined in our previous study regarding (99m)Tc-HABBN and the low in vivo metabolic stability determined in this study, is striking. This issue warrants further study of peptide-based radiopharmaceuticals.
authors.affiliation: Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: h.j.k.ananias@umcg.nl.
authors.forename: Hildo J K
authors.initials: HJ
authors.lastname: Ananias
authors.forename: Zilin
authors.initials: Z
authors.lastname: Yu
authors.forename: Hilde D
authors.initials: HD
authors.lastname: Hoving
authors.forename: Stefano
authors.initials: S
authors.lastname: Rosati
authors.forename: Rudi A
authors.initials: RA
authors.lastname: Dierckx
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Yan
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Jan
authors.initials: J
authors.lastname: Pruim
authors.forename: Marjolijn N
authors.initials: MN
authors.lastname: Lub-de Hooge
authors.forename: Wijnand
authors.initials: W
authors.lastname: Helfrich
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
authors.forename: Igle J
authors.initials: IJ
authors.lastname: de Jong
mesh_terms: D000368:Aged; D015119:Aminocaproic Acid / Q000737:chemistry*; D004355:Drug Stability; D005240:Feasibility Studies; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009943:Organophosphorus Compounds / Q000737:chemistry*; D015609:Organotechnetium Compounds / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D010865:Pilot Projects; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism; D011786:Quality Control; D018004:Receptors, Bombesin / Q000378:metabolism; D013451:Sulfonic Acids / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D010446:Peptide Fragments; D018004:Receptors, Bombesin; D013451:Sulfonic Acids; C555232:technetium 99m HYNIC-bombesin (7-14); C400058:triphenylphosphine-3,3',3''-trisulfonic acid; D005998:Glycine; D015119:Aminocaproic Acid; C100184:tricine
keywords: Bombesin; First-in-man; GRPR; Prostate cancer; SPECT/CT