Natural killer (NK) cells, which were first identified as lymphoid cells with lytic activity against tumor cells, play a relevant role in their detection and elimination without prior immunization. Recent advances highlighted how NK are a promising alternative to conventional T-cell based immunotherapy, but diagnostic tools to predict and evaluate therapeutic outcomes are lacking. Imaging can offer several approaches to address this issue. We focalized our research for the validation of a new radiopharmaceutical based on monoclonal antibodies (mAb) that target NK cells, in particular based on F(ab')2 fragments to detect NK cell trafficking. Radiolabelled anti-CD56 mAbs have favourable characteristics and showed to be an excellent choice for these aims as demonstrated in our pre-clinical studies. However, the main drawback in the use of whole mAbs is due to the response caused by production of human anti-murine antibodies (HAMAs). To overcome this limitation, the Fc region of the mAb can be cleaved to produce two Fab fragments bound together in a divalent structure referred to as the F(ab')2 fragment. Also, the shorter half-life of the F(ab')2 allows the use of radioisotopes with shorter half-life life (e.g. 68Ga) suitable for immune-PET that provides a better resolution and feasibility to human translation. The radiolabelled F(ab')2 fragment from anti-CD56 mAb could be an important diagnostic tool, both to predict and monitor the response to cancer immunotherapy.
