Evaluation of affibody molecule-based PNA-mediated radionuclide pretargeting: Development of an optimized conjugation protocol and 177 Lu labeling

摘要: Abstract Introduction We have previously developed a pretargeting approach for affibody-mediated cancer therapy based on PNA–PNA hybridization. In this article we further by optimizing the production of primary agent, Z HER2:342 -SR- HP1 , and labeling secondary HP2 with therapeutic radionuclide 177 Lu. also studied biodistribution profile Lu- in mice, evaluated vitro vivo. Methods The was NMRI mice compared to 111 In- . Pretargeting using HER2-expressing cell lines BT‐474 SKOV-3, vivo bearing SKOV-3 xenografts. Results conclusion Using an optimized protocol ligation time reduced from 15 h 30 min, yield increased 45% 70%. Lu-labeled binds specifically BT474 cells pre-treated shown more rapid blood clearance measured radioactivity 0.22 ± 0.1 0.68 ± 0.07%ID/g respectively, at 1 h p.i. contrast, no significant difference kidney uptake observed (4.47 ± 1.17 3.94 ± 0.58%ID/g p.i.). Co-injection either Gelofusine or lysine significantly (1.0 ± 0.1 1.6 ± 0.2, vs. 2.97 ± 0.87%ID/g controls 4 h accumulated xenografts BALB/C nu/nu when administered after injection Without pre-injection HP1, about 90-fold lower tumor (0.23 ± 0.08 20.7 ± 3.5%ID/g). tumor-to-kidney accumulation ratio almost 5-fold higher group pre-injected conclusion, be promising agent