68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

Abstract

DOTA-RGD peptide was successfully labelled with the generator-produced 68Ga. The tracer had reasonably good specific radioactivity (8.7 ± 1.1 GBq/μmol) and was quite stable in vivo. According to ex vivo biodistribution results, 68Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of 68Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio ± SD 1.4 ± 0.1, p = 0.0004). Conclusion We observed that 68Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques.

In vitro assessment of the dual-targeting behavior of a peptide-based magnetic resonance imaging contrast agent

“…Since the Arg-Gly-Asp (RGD) peptide is specific to α v β 3 (10,11), numerous applications based on the RGD/α v β 3 targeting delivery system have been reported in molecular imaging (12,13). Similarly, the Asn-Gly-Arg (NGR) peptide is a specific recognition sequence of CD 13 (14).…”

“…The peptide sequence was then coupled to the complex gadolinium (Gd)-1,4, 7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to investigate its efficacy as a tumor-targeting contrast agent. The contrast agent can target α v β 3 and CD 13 as a dual-targeting contrast agent. α v β 3 and CD 13 are tumor biomarkers; however, these proteins are not highly expressed in all tumor types.…”

“…The contrast agent can target α v β 3 and CD 13 as a dual-targeting contrast agent. α v β 3 and CD 13 are tumor biomarkers; however, these proteins are not highly expressed in all tumor types. If each of the RGD and NGR peptides in the dual-targeting contrast agent binds to α v β 3 -overexpressing and CD 13 -overexpressing tumor cells, respectively, then the contrast agent can detect both types of tumor, and thus the combination of RGD and NGR may improve tumor detection rates.…”

“…Since the Arg-Gly-Asp (RGD) peptide is specific to α v β 3 (10,11), numerous applications based on the RGD/α v β 3 targeting delivery system have been reported in molecular imaging (12,13). Similarly, the Asn-Gly-Arg (NGR) peptide is a specific recognition sequence of CD 13 (14). The NGR/CD 13 -based targeting delivery system is frequently reported in drug design for the treatment of cancer (15,16) and as an imaging system (17,18).…”

“…Integrin α v β 3 and aminopeptidase N (CD 13 ) are expressed in sprouting endothelial cells and in various tumor cells, but show restricted expression in normal cells, which renders them suitable receptors for tumor-targeting agents (9). Since the Arg-Gly-Asp (RGD) peptide is specific to α v β 3 (10,11), numerous applications based on the RGD/α v β 3 targeting delivery system have been reported in molecular imaging (12,13).…”