Radionuclide imaging of small-cell lung cancer (SCLC) using 99mTc-labeled neurotensin peptide 8–13

Zhang, Kaijun; An, Rui; Gao, Zairong; Zhang, Yongxue; Aruva, Mohan R.

doi:10.1016/j.nucmedbio.2006.03.003

« Previous Next »Nuclear Medicine and Biology
Volume 33, Issue 4 , Pages 505-512, May 2006

Radionuclide imaging of small-cell lung cancer (SCLC) using ^99mTc-labeled neurotensin peptide 8–13

Kaijun Zhang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
- Corresponding author. Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA. Tel.: +1 215 503 7879.
Rui An
- Department of Nuclear Medicine, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Zairong Gao
- Department of Nuclear Medicine, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Yongxue Zhang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Mohan R. Aruva
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA

Received 7 January 2006; received in revised form 23 February 2006; accepted 5 March 2006. published online 02 May 2006.

Abstract

Objectives

To prepare ^99mtechnetium (^99mTc)-labeled neurotensin (NT) peptide and to evaluate the feasibility of imaging oncogene NT receptors overexpressed in human small-cell lung cancer (SCLC) cells.

Methods

The NT analogue (Nα-His)Ac-NT(8–13) was synthesized such that histidine was attached at the N-terminus. The analogue was labeled with [^99mTc(H₂O)₃(CO)₃] at pH 7. ^99mTc-(Nα-His)Ac-NT(8–13) in vitro stability was determined by challenging it with 100 times the molar excess of DTPA, human serum albumin (HSA) and cysteine. The affinity, ^99mTc-(Nα-His)Ac-NT(8–13) binding to SCLC cell line NCI-H446, was studied in vitro. Biodistribution and imaging with ^99mTc-(Nα-His)Ac-NT(8–13) were performed at 4 and 12 h postinjection, and tissue distribution and imaging after receptor blocking were carried out at 4 h in nude mice bearing human SCLC tumor. Blood clearance was determined in normal mice.

Results

The affinity constant (K_d) of ^99mTc-(Nα-His)Ac-NT(8–13) to SCLC cells was 0.56 nmol/L. When challenged with 100 times the molar excess of DTPA, HSA or cysteine, more than 97±1.8% radioactivity remained as ^99mTc-(Nα-His)Ac-NT(8–13). Tumor-to-muscle ratio was 3.35±1.01 at 4 h and 4.20±1.35 at 12 h postinjection. The excretory route of ^99mTc-(Nα-His)Ac-NT(8–13) was chiefly through the renal pathway. In the receptor-blocking group treated with unlabeled (Nα-His)Ac-NT(8–13), tumor-to-muscle ratio at 4 h was 1.25±0.55.

Conclusion

The results suggest that ^99mTc-(Nα-His)Ac-NT(8–13) specifically binds to the SCLC cells and made ^99mTc-(Nα-His)Ac-NT(8–13) a desirable compound for further studies in planar or SPECT imaging of oncogene receptors overexpressed in SCLC cells.

Keywords: Neurotensin (NT) peptide, NT analogue, Small-cell lung cancer, ^99mTc