[Tc]-labeling and evaluation of a new linear peptide for imaging of glioblastoma as a αβ-positive tumor.

PURPOSE

In this study, we designed a new linear 6-Hydrazinonicotinamide (HYNIC)-conjugated peptide (HYNIC-KRWrNM) (M-6) and labeled with technetium-99m for gamma imaging of glioblastoma as a αβ-positive tumor. We evaluated tumor targeting ability of this radio-peptide and compared with previous Tc-labeled HYNIC-conjugated RGD analogue peptides.

PROCEDURES

One new linear peptide (HYNIC-KRWrNM) (M-6) was designed and labeled with technetium-99m in the presence of 2-[[1,3-dihydroxy-2-(hydroxymethyl) propan-2-yl] amino] acetic acid (Tricine)/Ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligand system. Then, this Tc-labeled peptide ([Tc]Tc-M-7) was evaluated for in vitro stability in saline and serum, specific binding assay, internalization, and binding affinity (K). In addition, we performed biodistribution study and planar imaging on nude mice bearing U87-MG xenograft as a αβ-positive tumor.

RESULTS

The radiochemical yield of [Tc]Tc-M-7 was obtained ˃95%. This Tc-labeled peptide remained stable and intact in saline solution after 24 h incubation. In addition, metabolic stability of this Tc-labeled peptide was obtained ˃60% after 4 h incubation in serum. The K value for [Tc]Tc-M-7 was obtained 5.2 ± 1.0 nM. Based on biodistribution results in nude mice bearing U87-MG xenograft, tumor/muscle activity ratio was 6.22 and decreased to 1.89 in blocking group at the same time point (4 h p.i.). The blocking experiment results also indicated that tumor uptake and kidney uptake were αβ-mediated. In comparison with previous HYNIC-conjugated RGD analogue peptides, kidneys had the highest uptake of this Tc-labeled peptide (52.29 ± 11.48 at 1.5 h p.i. and 27.04 ± 0.66%ID/g at 4 h p.i.). Finally, similar to previous Tc-labeled HYNIC-conjugated RGD analogue peptides, [Tc]Tc-M-7 showed acceptable tumor uptake after 4 h post-injection (based on ROI technique, target-to-background activity ratio = 3.80).

CONCLUSIONS

This small linear Tc-labeled peptide, with high affinity to αβ integrin, desirable water solubility, and cost efficient, demonstrates a potent tumor targeting ability as well as previous HYNIC-conjugated RGD analogue peptides. Hence, [Tc]Tc-M-7 can be of service to as a new candidate for early detection of αβ-positive tumors.