Radiolabelled cyclodextrins to detect cervical cancer: a preclinical feasibility study

Radiolabelled cyclodextrins targeting prostaglandin E2 (PGE2) seem promising candidates for positron emission tomography (PET)-based molecular imaging of cervical cancer. Here, we evaluated the performance of gallium-68-labelled 2-hydroxypropyl-β-cyclodextrin (HPβCD) and randomly methylated β-cyclodextrin (RAMEB) for the in vivo PET detection of cervical cancer. P-glycoprotein positive (Pgp+) KB-V-1 and P-glycoprotein negative (Pgp-) KB-3-1 cervical carcinoma xenografts of varying sizes (small-, medium-, large-sized) were established and subjected to [⁶⁸Ga]Ga-NODAGA-HPβCD and [⁶⁸Ga]Ga-DOTAGA-RAMEB PET imaging followed by ex vivo biodistribution and immunohistochemical (IHC) analysis of PGE2 and Pgp expression. In line with the IHC results, PET data revealed the capability of both radiotracers to reliably detect each tumor types independent of tumor size. Nevertheless, the modest increase in uptake observed with increasing size may indicate enhanced tumor aggressiveness and angiogenic activity. Comparable radiotracer accumulation in MDR-positive and MDR-negative tumors suggests that HPβCD and RAMEB derivatives are unlikely to serve as substrates of Pgp enabling tumor detection across different tumor types. Collectively, our findings demonstrate that radiolabelled cyclodextrins are promising PET tracers for the in vivo detection of cervical cancer, irrespective of tumor size and Pgp expression.