⁶⁴Cu tumor labeling with hexadentate picolinic acid-based bispidine immunoconjugates

Area of Science:

• Radiopharmaceutical Chemistry
• Nuclear Medicine
• Coordination Chemistry

Background:

• Bispidine ligands are investigated for their strong binding affinity to Cu(II).
• Picolinate appended bispidine derivatives offer potential for radiolabeling applications.

Purpose of the Study:

• To radiopharmacologically characterize two isomeric picolinate-appended bispidine ligands.
• To evaluate the stability and biodistribution of copper-64 (⁶⁴Cu)-bispidine complexes.
• To develop targeted radiotracers for molecular imaging of cancer.

Main Methods:

• Quantitative radiolabeling of bispidine ligands with ⁶⁴Cu.
• In vitro stability assays using EDTA, cyclam, human serum, and SOD.
• In vivo biodistribution studies in Wistar rats.
• Small animal PET imaging in tumor-bearing mice using targeted radiotracers.

Main Results:

• High radiochemical purity and yield achieved for ⁶⁴Cu-bispidine complexes (>200 MBq/nmol).
• Complexes demonstrated high stability and inertness in challenge experiments.
• Rapid renal elimination observed for ⁶⁴Cu-labeled chelates.
• Targeted ⁶⁴Cu-labeled tumor modules showed specific accumulation in PSCA- and FAP-overexpressing tumors.

Conclusions:

• Picolinate-appended bispidine ligands are suitable for developing stable ⁶⁴Cu-based radiopharmaceuticals.
• The developed ⁶⁴Cu-labeled tumor targeting modules exhibit promising specificity for molecular imaging of prostate cancer and fibrosarcoma.