Bispecific Her2 × cotinine antibody in combination with cotinine–(histidine)2–iodine for the pre-targeting of Her2-positive breast cancer xenografts

Abstract

With these findings, we conclude that the tandem scFv Fc fusion protein and cotinine hapten system have the potential to be applied in PRIT.

Immunoglobulin Fc-fused, neuropilin-1-specific peptide shows efficient tumor tissue penetration and inhibits tumor growth via anti-angiogenesis

“…The FaDu tumor xenografts were allowed to grow until they reached ~400 mm 3 in volume, and then the mice were injected IV with 18.5 MBq (500 μCi/60 μg per mouse) of 125 I-labeled protein in PBS via the tail vein. Whole-body radioactivity was measured at 0, 0.5, 1, 2, 4, 6, 12, 24, 48, 72, and 96 h after injection with SPECT (NanoSPECT, Bioscan) [29]. The data were reported as the mean percentage of remaining whole-body radioactivity, with the initial radioactivity at injection set at 100%.…”

“…We determined pharmacokinetic profiles of Fc or Fc-TPP11 by measuring whole-body radioactivity using single-photon emission computed tomography (SPECT) [29,30]. Fc and Fc-TPP11 were labeled with 125 I using the chloramine-T method, as described previously [29,30].…”

“…Fc and Fc-TPP11 were labeled with 125 I using the chloramine-T method, as described previously [29,30]. Six-week-old female BALB/c athymic nude mice were fed Lugol's solution for 2 weeks to block thyroid uptake before protein injection and injected subcutaneously with FaDu cells (5 × 10 6 cells/mouse) in the right thigh.…”

Addressing challenges of heterogeneous tumor treatment through bispecific protein-mediated pretargeted drug delivery

“…developed an early pretargeted imaging approach using a murine tumor model through the injection of anti-chelate antibodies, followed by the administration of a radiolabel [99]. Since then, a number of antibodies against various haptens have been utilized for binding to effector molecules, including anti-DTPA complex [100, 101], anti-peptide [102–104], anti-methotrexate [105], and anti-cotinine antibodies [106]. In addition to bispecific antibodies [101, 102, 107], a range of antibody fragments and derivatives have been developed as pretargeting BsPs [71, 106, 108].…”

“…Since then, a number of antibodies against various haptens have been utilized for binding to effector molecules, including anti-DTPA complex [100, 101], anti-peptide [102–104], anti-methotrexate [105], and anti-cotinine antibodies [106]. In addition to bispecific antibodies [101, 102, 107], a range of antibody fragments and derivatives have been developed as pretargeting BsPs [71, 106, 108]. Most antibodies, including those used to capture radioisotope-carrying effector molecules in PRIT, exhibit nanomolar to high picomolar affinity (K D ∼10 −7 –10 −10 M) for the antigen target on the surface of cancer cells [98, 105, 109].…”