A Systematic Comparative Evaluation of ⁶⁸Ga-Labeled RGD Peptides Conjugated with Different Chelators / 대한핵의학회잡지

PURPOSE: The present paper reports a systematic study on the effect of bifunctional chelators (BFC) namely, NOTA, DOTA, and DTPA, on the radiochemical formulation, in vitro stability, and in vivo biological properties of ⁶⁸Ga-labeled RGD peptide derivatives.METHODS: The three RGD conjugates namely, NOTA-Bn-E-[c(RGDfk)]₂, DOTA-Bn-E-[c(RGDfk)]₂, and DTPA-Bn-E-[c(RGDfk)]₂ were radiolabeled with ⁶⁸Ga and the radiolabeling was optimized with respect to the ligand amount, radiolabeling time, and temperature. Further, the ⁶⁸Ga complexes were assessed for their in vitro and in vivo stabilities. The biodistribution studies of the three radiolabeled conjugates were carried out in C57BL/6 mice bearing melanoma tumor at 30 min and 1 h post-adimistration.RESULTS: NOTA-Bn-E-[c(RGDfk)]₂ could be radiolabeled with ⁶⁸Ga at room temperature while DOTA-Bn-E-[c(RGDfk)]₂ and DTPA-Bn-E-[c(RGDfk)]₂ were radiolabeled at high temperature. ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ was found to be the most kinetically rigid in in vitro stability assay. The uptake of the three radiolabeled peptide conjugates in melanoma tumor was comparable at 1 h post-administration (NOTA; DOTA; DTPA (% I.D./g):: 2.78 ± 0.38; 3.08 ± 1.1; 3.36 ± 0.49). However, the tumor/background ratio of ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ was the best amongst the three radiotracers. ⁶⁸Ga-complexes of NOTA-Bn-E-[c(RGDfk)]₂ and DOTABn-E-[c(RGDfk)]₂ showed excellent in vivo stability while ⁶⁸Ga-DTPA-Bn-E-[c(RGDfk)]₂ showed significant metabolic degradation.CONCLUSION: These studies show that ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ would be the most appropriate ⁶⁸Ga-labeled radiotracer and the most amenable for kit formulation.

Radio-graphene in Theranostic Perspectives / 대한핵의학회잡지

Owing to its unique physicochemical properties such as high surface area, notable biocompatibility, robust mechanical strength, high thermal conductivity, and ease of functionalization, 2D-layered graphene has received tremendous attention as a futuristic nanomaterial and its-associated research has been rapidly evolving in a variety of fields.With the remarkable advances of graphene especially in the biomedical realm, in vivo evaluation techniques to examine in vivo behavior of graphene are largely demanded under the hope of clinical translation. Many different types of drugs such as the antisense oligomer and chemotherapeutics require optimal delivery conveyor and graphene is now recognized as a suitable candidate due to its simple and high drug loading property. Termed as ‘ radio-graphene’, radioisotope-labeled graphene approach was recently harnessed in the realm of biomedicine including cancer diagnosis and therapy, contributing to the acquisition of in vivo information for targeted drug delivery. In this review, we highlight current examples for bioapplication of radiolabeled graphene with brief perspectives on future strategies in its extensive bio- or clinical applications.