Radionuclide imaging of small-cell lung cancer (SCLC) using 99mTc-labeled neurotensin peptide 8-13.
OBJECTIVE
To prepare 99m technetium (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 (Nalpha-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-(Nalpha-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-(Nalpha-His)Ac-NT(8-13) binding to SCLC cell line NCI-H446, was studied in vitro. Biodistribution and imaging with 99mTc-(Nalpha-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 (Kd) of 99mTc-(Nalpha-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-(Nalpha-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-(Nalpha-His)Ac-NT(8-13) was chiefly through the renal pathway. In the receptor-blocking group treated with unlabeled (Nalpha-His)Ac-NT(8-13), tumor-to-muscle ratio at 4 h was 1.25+/-0.55.


CONCLUSIONS
The results suggest that 99mTc-(Nalpha-His)Ac-NT(8-13) specifically binds to the SCLC cells and made 99mTc-(Nalpha-His)Ac-NT(8-13) a desirable compound for further studies in planar or SPECT imaging of oncogene receptors overexpressed in SCLC cells.
Zhang
Kaijun
K
Department of Nuclear Medicine, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. kaijunzhang99@hotmail.com
An
Rui
R
Gao
Zairong
Z
Zhang
Yongxue
Y
Aruva
Mohan R
MR
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D009496:Neurotensin / Q000737:chemistry / Q000493:pharmacokinetics*; D009928:Organ Specificity; D010446:Peptide Fragments / Q000737:chemistry / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D018028:Receptors, Neurotensin / Q000378:metabolism*; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D018028:Receptors, Neurotensin; D009496:Neurotensin; C054381:neurotensin (8-13); D013667:Technetium