Pre-clinical dosimetry for ¹²⁴I-CPD-1028 immunoconjugate targeting IGF-1R.

Objectives Objectives: Insulin-like growth factor-1 receptor (IGF-1R) was identified as an oncogenic protein associated with multiple cancer types. Figitumumab (F), developed by Pfizer, was a Phase 3 human mAb therapeutic targeting IGF-1R. F binds with high affinity to target-expressing tumour cells and is rapidly internalized. Herein we describe pre-clinical dosimetry data for ¹²⁴I-CPD-1028, a novel F-based iodine-residualizing radioimmunoconjugate suitable for imaging and radiotherapy.

Methods Methods: F was indirectly radioiodinated with 124-I by iododestannylation of CPD-1022 residualing synthon followed by NHS-conjugation to produce ¹²⁴I-CPD-1028. A biodistribution study with excreta collection was performed using nine groups of male and female CD-1 mice (4 each/group). Mice received a single 50 μCi dose of ¹²⁴I-CPD-1028 and were sacrificed for tissue collection after 0.17, 1, 2, 4, 7, 10, 14, 18 and 21 days. Thyroid blocking was not used. Human organ dosimetry was extrapolated from the mouse data.

Results Results: Dosimetry analysis identified the critical dose organs to be the lower large intestine wall (1.90 mGy/MBq), thyroid (1.90 mSv/MBq), upper large intestine wall (1.10 mSv/MBq), osteogenic cells (0.70 mSv/MBq), small intestine (0.70 mSv/MBq) and urinary bladder wall (0.70 mSv/MBq). Organ absorbed dose value estimates were similar for males and females, except for the heart wall, liver, lungs, spleen and thyroid (all ~10% higher for females). The effective dose per unit administered activity was calculated to be 0.78 mSv/MBq for the adult male and 0.81 mSv/MBq for the adult female.

Conclusions Conclusion: Dosimetry studies yielded an estimated human effective dose per unit activity of 0.78 mSv/MBq and 0.81 mSv/MBq for human adult males and females respectively, which would provide a total radiation dose of 29 mSv and 30 mSv respectively following a 37 MBq dose of ¹²⁴I-CPD-1028.