18F-FLT and 18F-ISO-1 PET/CT have the potential to serve as a clinically translatable approach for predicting and monitoring response to combinatorial CDK4/6 inhibitors and endocrine therapy in patients with ER+ breast cancer, with 18F-FLT measuring immediate changes in the S-phase as a predominate effect of targeting CDK4/6, providing a very early prediction of tumor response, and 18F-ISO-1 assessing delayed changes reflecting cell-cycle arrest and transition to quiescence (35). Here, ESR1 is linked to breast cancer.