99mTc-Labeled RGD-BBN Peptide for Small-Animal SPECT/CT of Lung Carcinoma

We recently designed and synthesized a Gluc(RGDyK)-bombesin (RGD-BBN) heterodimeric peptide exhibiting a dual integrin alpha(v)beta(3) and gastrin-releasing peptide receptor (GRPR) targeting property. In this study, we investigated whether Tc-99m-labeled RGD-BBN peptide could be used for the non-invasive 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 Tc-99m 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 Tc-99m-HYNIC(tricine)(TPPTS)-RGD-BBN (Tc-99m-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 alpha(v)beta(3) and GRPR binding capacity. Tc-99m-RGD-BBN was prepared with a high radiochemical purity (>98%), and it exhibited specific tumor imaging with high contrast to the contralateral background. Tc-99m-RGD-BBN was superior to F-18-FDG for distinguishing lung carcinoma from inflammation. The uptake of Tc-99m-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 Tc-99m-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 Tc-99m-RGD-BBN can specifically detect the LLC pulmonary metastases. Our results suggested that SPECT/CT with Tc-99m-RGD-BBN would provide an effective approach for the noninvasive detection of lung cancer.