Radiolabeled RGD (
Arg-Gly-Asp) and
bombesin (BBN) radiotracers that specifically target
integrin alpha(v)beta(3) and
gastrin releasing peptide receptor (GRPR) are both promising
radiopharmaceuticals for
tumor imaging. We recently designed and synthesized a RGD-BBN heterodimeric
peptide with both RGD and BBN motifs in one single molecule. The (18)F-labeled RGD-BBN heterodimer exhibited dual
integrin alpha(v)beta(3) and GRPR targeting in a PC-3
prostate cancer model. In this study we investigated whether radiolabeled RGD-BBN tracers can be used to detect
breast cancer by using microPET. Cell binding assay demonstrated that the high GRPR expressing
breast cancer cells typically express low to moderate level of
integrin alpha(v)beta(3), while high
integrin alpha(v)beta(3) expressing
breast cancer cells have negligible level of GRPR. We labeled RGD-BBN heterodimer with three positron emitting
radionuclides (18)F, (64)Cu, and (68)Ga and investigated the corresponding PET radiotracers in both orthotopic T47D (GRPR(+)/low
integrin alpha(v)beta(3)) and MDA-MB-435 (GRPR(-)/
integrin alpha(v)beta(3)(+))
breast cancer models. The three radiotracers all possessed in vitro dual
integrin alpha(v)beta(3) and GRPR binding affinity. The advantages of the RGD-BBN radiotracers over the corresponding BBN analogues are obvious for imaging MDA-MB-435 (GRPR(-)/
integrin alpha(v)beta(3)(+))
tumor. (18)F-FB-PEG(3)-RGD-BBN showed lower
tumor uptake than (64)Cu-NOTA-RGD-BBN and (68)Ga-NOTA-RGD-BBN but was able to visualize
breast cancer tumors with high contrast. Synthesis of (64)Cu-NOTA-RGD-BBN and (68)Ga-NOTA-RGD-BBN is much faster and easier than (18)F-FB-PEG(3)-RGD-BBN. (64)Cu-NOTA-RGD-BBN showed prolonged
tumor uptake but also higher liver retention and kidney uptake than (68)Ga-NOTA-RGD-BBN and (18)F-FB-PEG(3)-RGD-BBN. (68)Ga-NOTA-RGD-BBN possessed high
tumor signals but also relatively high background uptake compared with the other two radiotracers. In summary, the prosthetic labeling groups,
chelators, and
isotopes all have a profound effect on the
tumor targeting efficacy and in vivo kinetics of the RGD-BBN tracers for dual
integrin and GRPR recognition. Further development of suitably labeled RGD-BBN tracers for PET imaging of
cancer is warranted.