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

ObjectivesTo 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.MethodsThe 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.ResultsThe affinity constant (Kd) 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.ConclusionThe 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.