title: [99mTc]demotensin VI: biodistribution and initial clinical results in tumor patients of a pilot/phase I study.
abstract: OBJECTIVE
  Neurotensin subtype 1 receptor overexpression is found in a variety of human tumors. The aim of this pilot/phase I study was to assess the safety profile, pharmacokinetics, and imaging characteristics of (99m)Tc-Demotensin VI in tumor patients.
  
  
  METHODS
  Scintigraphy with (99m)Tc-Demotensin VI was performed in 14 patients (2 female and 12 male) with advanced tumor stages. The diagnoses were pancreatic adenocarcinoma (n=4), small cell lung cancer (SCLC) (n=4), non-small cell lung cancer (NSCLC) (n=4), and colon carcinoma (n=2). Patients were injected with 500-550 MBq (99m)Tc-Demotensin VI. Blood samples were taken at various time points and urine was also collected up to 24 hours post-injection (p.i.) Planar images were acquired at 15-30 minutes, 1-2 hours, 4 hours, and 24 hours p.i. with additional SPECT imaging at 4 hours.
  
  
  RESULTS
  Radiochemical purity always exceeded 95% up to 4 hours. Urinary and blood excretion was rapid with 5.05% ID (mean: n=5) in plasma after 4 hours. No side effects were observed after injection of (99m)Tc-Demotensin VI. Focal tracer accumulation was observed in 3 patients with brain metastases due to NSCLC, although specificity of this uptake could not be proven. Further, no tumor-related findings were observed. Although stability tests in human plasma revealed that (99m)Tc-Demotensin VI remained intact up to 2 hours incubation, ex vivo urine analysis indicated rapid metabolism.
  
  
  CONCLUSIONS
  (99m)Tc-Demotensin VI was well tolerated by patients and showed favorable pharmacokinetics; however, tumor targeting was limited to brain metastases. Further studies on stability issues and receptor characterization in tumors are warranted to introduce neurotensin receptors (NTSR) imaging into the clinic.
authors: Department of Nuclear Medicine and Endocrinology, General Hospital of Linz, Linz, Austria.
authors: Michael
authors: M
authors: Gabriel
authors: Clemens
authors: C
authors: Decristoforo
authors: Ewald
authors: E
authors: Wöll
authors: Wolfgang
authors: W
authors: Eisterer
authors: Berthold
authors: B
authors: Nock
authors: Theodosia
authors: T
authors: Maina
authors: Roy
authors: R
authors: Moncayo
authors: Irene
authors: I
authors: Virgolini
mesh_terms: D000368:Aged; D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009496:Neurotensin / Q000009:adverse effects / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D010865:Pilot Projects; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics*; D018028:Receptors, Neurotensin / Q000378:metabolism
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin