Affibody-based imaging of HER3 is a promising approach for patient stratification. We investigated the influence of a hydrophilic HEHEHE-tag ((HE) 3 -tag) and two different gallium-68/chelator-complexes on the biodistribution of Z 08698 with the aim to improve the tracer for PET imaging. Affibody molecules (HE) 3 -Z 08698 -X and Z 08698 -X (X = NOTA, NODAGA) were produced and labeled with gallium-68. Binding specificity and cellular processing were studied in HER3-expressing human cancer cell lines BxPC-3 and DU145. Biodistribution was studied 3 h p.i. in Balb/c nu/nu mice bearing BxPC-3 xenografts. Mice were imaged 3 h p.i. using microPET/CT. Conjugates were stably labeled with gallium-68 and bound specifically to HER3 in vitro and in vivo. Association to cells was rapid but internalization was slow. Uptake in tissues, including tumors, was lower for (HE) 3 -Z 08698 -X than for non-tagged variants. The neutral [ 68 Ga]Ga-NODAGA complex reduced the hepatic uptake of Z 08698 compared to positively charged [ 68 Ga]Ga-NOTA-conjugated variants. The influence of the chelator was more pronounced in variants without (HE) 3- tag. In conclusion, hydrophilic (HE) 3 -tag and neutral charge of the [ 68 Ga]Ga-NODAGA complex promoted blood clearance and lowered hepatic uptake of Z 08698 . [ 68 Ga]Ga-(HE) 3 -Z 08698 -NODAGA was considered most promising, providing the lowest blood and hepatic uptake and the best imaging contrast among the tested variants.
- Molecular imaging
ASJC Scopus subject areas
- Molecular Biology
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry