Ga-68 labeled neurotensin NTS₁R ligands: Is a separation of the labeling precursor advantageous for tumor uptake?

Ziel/Aim Recently, we described new Ga-68 labeled neurotensin NTS₁R PET ligands [1]. One peptidic PET ligand with high NTS₁R affinity (K_i=1.2 nM) was used to explore whether separation of the PET ligand from the precursor of comparable NTS₁R affinity (K_i=5.9 nM) affects tracer uptake into the tumor.

Methodik/Methods Radiolabeling of the DOTA-conjugated precursor (14.7 nmol) was done fully automated using a standard procedure [2] unable to separate tracer from remaining precursor. After C18-cartridge based processing of the reaction mixture, Ga-68-labeled peptide and residual precursor were eluted with ethanol. The eluate was further formulated directly or after separation of precursor and tracer by RP-HPLC. Biodistribution studies were performed in nude mice bearing subcutaneous HT-29 tumors.

Ergebnisse/Results The purified NTS₁R PET ligand, exhibiting high polarity (logD_7.4 -3.06), was obtained in a radiochemical purity of>92% within 80 min (no separation of precursor) or 140 min (separated from precursor). When studied in mice without precursor separation, a tumor-to-muscle ratio (TMR) of 9.7 was determined. Separation of residual precursor from the PET tracer led to higher specific activity and an almost doubled TMR of 16. Blocking experiments confirmed an NTS1R-mediated uptake. Urine analysis 45 min p.i. revealed that 97% of the activity accounted for the intact tracer.

Schlussfolgerungen/Conclusions Our study demonstrates that especially in the case of very high affinity PET ligands, a separation of a high-affinity PET ligand from residual high affinity precursor should be considered. Due to the short half-life of Ga-68 and for reasons of practicability, a compromise must be made between acceptable radioactive decay during separation of the tracer and improved uptake of the purified tracer into the tumor.

• Literatur/References

• 1 Schindler et al. Cancers 2022; 14: 4922
• 2 Martin et al. Nucl Med Mol Biol 2014; 42: 84

Publication History

Article published online:
30 March 2023