Aim: Here, we established a reliable strategy for generation and characterization of targeted radiolabeled exosomes for the detection of HER2-positive cells quantitatively. Materials & methods: Targeted exosomes (T-exos) were radiolabeled by two different radiotracers, [^99mTc]Tc-HMPAO or [¹¹¹In]In-oxine. The labeling efficiency and stability were assessed using exosome exclusive spin columns. HER2-positive and -negative cells were treated with [¹¹¹In]In-oxine-exosomes after 3 and 24 h. Results: [¹¹¹In]In-oxine labeling did not change the binding ability and general features of the exosomes. With [¹¹¹In]In-oxine, 70% labeling efficiency and 78% radiochemical stability over 24 h were achieved. [¹¹¹In]In-oxine-T-exos showed greater uptake by HER2-positive cells compared with untargeted exosomes. Conclusion: [¹¹¹In]In-oxine-T-exos could potentially be used as an effective imaging tool for HER2 expression.