[99mTc]demotensin VI: biodistribution and initial clinical results in tumor patients of a pilot/phase I study.

Abstract

PURPOSE:

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.

CONCLUSION:

(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: Michael Gabriel, Clemens Decristoforo, Ewald Wöll, Wolfgang Eisterer, Berthold Nock, Theodosia Maina, Roy Moncayo, Irene Virgolini
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 26 Issue 5 Pg. 557-63 (Oct 2011) ISSN: 1557-8852 [Electronic] United States
• PMID: 21883013 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Organotechnetium Compounds
• Radiopharmaceuticals
• Receptors, Neurotensin
• neurotensin type 1 receptor
• Neurotensin

Topics

• Aged
• Animals
• Brain Neoplasms (diagnostic imaging, metabolism, secondary)
• Carcinoma, Non-Small-Cell Lung (diagnostic imaging, metabolism, pathology)
• Female
• Humans
• Lung Neoplasms (diagnostic imaging, metabolism, pathology)
• Male
• Mice
• Middle Aged
• Neoplasms (diagnostic imaging, metabolism)
• Neurotensin (adverse effects, pharmacokinetics)
• Organotechnetium Compounds (adverse effects, chemistry, pharmacokinetics)
• Pilot Projects
• Radionuclide Imaging
• Radiopharmaceuticals (adverse effects, pharmacokinetics)
• Receptors, Neurotensin (metabolism)