99mTc-labeled RGD-BBN peptide for small-animal SPECT/CT of lung carcinoma

Mol Pharm. 2012 May 7;9(5):1409-17. doi: 10.1021/mp200661t. Epub 2012 Apr 11.

Abstract

We recently designed and synthesized a Glu-c(RGDyK)-bombesin (RGD-BBN) heterodimeric peptide exhibiting a dual integrin α(v)β(3) and gastrin-releasing peptide receptor (GRPR) targeting property. In this study, we investigated whether (99m)Tc-labeled RGD-BBN peptide could be used for the noninvasive detection of lung carcinoma by using small-animal single-photon emission computed tomography (SPECT)/CT. RGD-BBN peptide was conjugated with 6-hydrazinonicotinyl (HYNIC) and then radiolabeled with (99m)Tc using tricine and TPPTS as the coligands (TPPTS = trisodium triphenylphosphine-3,3',3"-trisulfonate). The biodistribution, planar gamma imaging, and small-animal SPECT/CT studies of (99m)Tc-HYNIC(tricine)(TPPTS)-RGD-BBN ((99m)Tc-RGD-BBN) were performed in C57/BL6 mice bearing Lewis lung carcinoma (LLC) or bearing both inflammation and LLC. HYNIC-RGD-BBN possessed a dual integrin α(v)β(3) and GRPR binding capacity. (99m)Tc-RGD-BBN was prepared with a high radiochemical purity (>98%), and it exhibited specific tumor imaging with high contrast to the contralateral background. (99m)Tc-RGD-BBN was superior to (18)F-FDG for distinguishing lung carcinoma from inflammation. The uptake of (99m)Tc-RGD-BBN in LLC xenografts was 2.69 ± 0.66% ID/g at 1 h postinjection (p.i.) and was decreased to 1.99 ± 0.61% ID/g at 2 h p.i. The inflammation uptake of (99m)Tc-RGD-BBN was 1.20 ± 0.32% ID/g at 1 h and 0.56 ± 0.17% ID/g at 2 h p.i., respectively. High pancreas uptake (25.76 ± 5.49%ID/g and 19.56 ± 6.78% ID/g at 1 and 2 h p.i., respectively) was also found due to the high GRPR expression of this organ. Small-animal SPECT/CT using (99m)Tc-RGD-BBN can specifically detect the LLC pulmonary metastases. Our results suggested that SPECT/CT with (99m)Tc-RGD-BBN would provide an effective approach for the noninvasive detection of lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bombesin / chemistry*
  • Carcinoma / diagnosis*
  • Carcinoma, Lewis Lung / diagnosis
  • Cell Line, Tumor
  • Female
  • Humans
  • Lung Neoplasms / diagnosis*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oligopeptides / chemistry*
  • Organotechnetium Compounds* / chemistry
  • Peptides* / chemistry
  • Radiopharmaceuticals* / chemistry
  • Tomography, Emission-Computed, Single-Photon / methods*
  • Tomography, X-Ray Computed / methods*

Substances

  • Oligopeptides
  • Organotechnetium Compounds
  • Peptides
  • Radiopharmaceuticals
  • arginyl-glycyl-aspartic acid
  • Bombesin