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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 ^99mTc-Demotensin VI in tumor patients.

Methods:

Scintigraphy with ^99mTc-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 ^99mTc-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 ^99mTc-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 ^99mTc-Demotensin VI remained intact up to 2 hours incubation, ex vivo urine analysis indicated rapid metabolism.

Conclusion:

^99mTc-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.

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[ 99m Tc]Demotensin VI: Biodistribution and Initial Clinical Results in Tumor Patients of a Pilot/Phase I Study

Abstract

Purpose:

Methods:

Results:

Conclusion:

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References