Chelator free Ga-68/Gd co-labeling ultra-small gold nanorod for colorectal cancers PET-MRI diagnosis and image-guided radiotherapy

Introduction: As one of cancers with the highest incidence and mortality, colorectal cancers have shown a significant increase of incidence rate in China recently. For colon cancer, exact local staging at the time of diagnosis is essential and is the basis for requirement of neoadjuvant treatment. Thus, imaging technique especially PET-MRI imaging with ultra-high sensitivity and soft tissues resolution is recognized as one of the best techniques for diagnosis of colorectal cancers. To improve the sensitivity of PET-MRI imaging furtherly, it is necessary to use PET-MRI contrast agent during imaging.

Methods: One-step seeded growth method was used to synthesize ultra-small AuNRs (UGNRs). As-prepared UGNRs was first coated with polydopamine. Then, itG Ge-68/Ga-68 generator eluted radioisotope ⁶⁸Ga and GdCl₃ were immobilized on the surface of PDA-coated UGNRs by simple mixing the substances with the nanoparticles. Subsequently, a mixture of a negatively charged 12-mercaptoundecanoic acid (MUA) and a positively charged (11-mercaptodecyl) trimethylammonium bromide (TMA) with a mole ratio of 1:1 was self-conjugated by cross-linking the sulfhydryl group and by forming the self-assembled monolayer on the surface of probes. The final products (designated as ⁶⁸Gd-PDA@UGNRs) were carefully characterized and its efficacy for tumor imaging (PET-MRI, photoacoustic) and therapy (radiosensitization therapy) were evaluated. Results and Discussion: The size of UGNRs was 2.41 ± 1.01 nm in diameter and 6.12 ± 1.22 nm in length (aspect ratio of ∼2.5). The probe has a significant absorption at the wavelength about 520 nm. It self-aggregated at pH ≍ 6.0 accurately. PET-MRI and photoacoustic imaging showed that the probe could be significantly enriched in the tumor area.The radiosensitization therapy indicated that 68Gd-PDA@UGNRs probe could inhibit the growth of solid tumor effectively.

Conclusions: In this project, we aim to construct a theranostic probe for the diagnosis and radiotherapy of colorectal cancers based on the characteristics of PET-MRI imaging. We first synthesized ultra-small gold nanorods (UGNRs) with a size of 5 nm, and chelator free co-labeled the radioisotope ⁶⁸Ga and MRI contrast molecule Gd with the polydopamine coating on the surface of UGNRs. With the conjugation of acidic tumor microenvironment responded ligands, we hope the probe may able to specifically accumulate to tumor regions. With PET-MRI imaging, the lesion edge can be accurately distinguished, the tumor progression can be monitored, and the local radiotherapy sensitization treatment to tumor regions can be guided. In summary, this multi-modal theranostic probe could distinguish the lesion edge accurately and monitor tumor progression via PET-MRI imaging technique to improve treatment of colon cancer. Acknowledgements: This work was supported by grants from NSFC (81901804, 91959125), Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission (20JC1411900, GYY).