The combination of Positron Emission Tomography (PET) and the single chain fragment variable (scFv) provides a unique solution for PET imaging and drug development. scFv have faster pharmacokinetics while retaining the high specificity and high target affinity by only keeping the antigen-binding domain. PET imaging with scFv will benefit from this faster pharmacokinetics which matches the more accessible but short-lived PET radionuclide such as 68Ga. On the other hand, the high sensitivity of PET imaging could help reveal the unique pharmacokinetics of the drug conjugated scFv and accelerate its application.

With these two advantages, a novel anti-HER2 scFv TCT1067 was investigated for PET imaging through trans-cyclooctene (TCO)/tetrazine based 68Ga labelling. In addition, the fragment-drug conjugate (FDC) MMAF-TCT1067 were also labelled by 68Ga for better understanding of its pharmacokinetics. A series of the TCT1067 conjugates were synthesized and radiolabelled with 68Ga while conserving the high specificity and high binding affinity. Based on the successful radiolabelling, a comparative PET study of the 68Ga labelled TCT1067 and MMAF-TCT1067 was carried out for the first time. Using the highly sensitive PET imaging, the distinctive early pharmacokinetics between the TCT1067 and the MMAF-TCT1067 were revealed.