MicroPET imaging of breast cancer with 68Ga-labeled RGD-Bombesin heterodimer

Objectives Radiolabeled RGD and bombesin (BBN) peptides that specifically target integrin α_vβ₃ and GRPR are both promising for tumor imaging. We recently synthesized a RGD-BBN heterodimer with both the RGD and BBN motifs in one molecule. The ¹⁸F labeled RGD-BBN exhibited dual-receptor targeting property both in vitro and in vivo. We investigated that whether generator-eluted ⁶⁸Ga (t_1/2 =68 min) labeled RGD-BBN can be used to detect the breast tumors using microPET.

Methods RGD-BBN was conjugated with NOTA and labeled with ⁶⁸Ga. The cell uptake and in vivo tumor targeting efficacy of ⁶⁸Ga-NOTA-RGD-BBN were tested in MDA-MB-435 (GRPR^-/integrin α_vβ₃⁺) and T47D (GRPR⁺/integrin α_vβ₃ low expression) orthotopic breast cancer models.

Results NOTA-RGD-BBN possessed comparable in vitro integrin α_vβ₃ binding affinity with NOTA-RGD and comparable GRPR binding affinity with NOTA-BBN. ⁶⁸Ga-NOTA-RGD-BBN had significantly higher %ID/g tumor uptake (2.85 ± 0.79 for T47D, 2.24 ± 0.73 for MDA-MB-435) compared with ⁶⁸Ga-NOTA-RGD (1.22 ± 0.48 for T47D, 1.48 ± 0.55 for MDA-MB-435) and ⁶⁸Ga-NOTA-BBN (2.35 ± 0.86 for T47D, 0.45 ± 0.08 for MDA-MB-435) in both the two breast tumor models at 1 h. ⁶⁸Ga-NOTA-RGD-BBN showed high contrast tumor imaging in both T47D and MDA-MB-435 tumors, while ⁶⁸Ga-NOTA-BBN can only detect the GRPR-positive T47D tumors, and the tumor uptake of ⁶⁸Ga-NOTA-RGD was very low in both models.

Conclusions The convenient synthesis, improved in vivo kinetics and dual-receptor recognition properties of ⁶⁸Ga-NOTA-RGD-BBN over its RGD and BBN analogs make it useful to detect cancers with both or either receptor expression patterns.