The temporary inhibition of dynamin-mediated endocytosis of monoclonal antibody (mAb)-receptor complexes using prochlorperazine (PCZ) leads to clustering and increased cell surface retention, improving mAb-mediated antibody dependent cell cytotoxicity (ADCC) (doi: 10.1016/j.cell.2020.02.019). This in turn leads to improved efficacy of ADCC-mediating antibodies in cancer therapy. Pre-clinical studies by our research group have demonstrated that the effect of dynamin inhibition in vivo is highly reversible. The idea of temporary and reversible dynamin inhibition in vivo opens opportunities to not only improve mAb-mediated ADCC, but also delivery of antibody-drug conjugates (ADCs) and radioligand therapy (RLT). Whilst it may seem contradictory to inhibit endocytosis of molecular targets, a mechanism which ADCs/RLTs require for the delivery of drug/radiation payloads to the endosomes, temporary inhibition of endocytosis can potentially increase binding and accumulation of ADC/RLT-target complexes on the cell surface and allow synchronous endosomal delivery of drugs. We show upon pharmacological reversal of endocytosis inhibition a rapid wave of endocytosis occurs which serves to deliver an increased payload of ADCs/RLTs, thus improving the efficacy of ADCs/RLTs. Using PET/CT, live ex-vivo immunofluorescence uptake assays and pre-clinical murine models, we demonstrate how temporary inhibition of endocytosis using prochlorperazine affects uptake of prostate membrane specific antigen (PSMA)-targeted therapies in prostate cancer models and ADCs in pancreatic ductal adenocarcinoma (PDAC) models.