⁶⁸Ga- and ²¹¹At-Labeled RGD Peptides for Radiotheranostics with Multiradionuclides

Abstract

Probes for radiotheranostics could be produced by introducing radionuclides with similar chemical characteristics into the same precursors. We recently developed an 211At-labeled RGD peptide and a corresponding radioiodine-labeled RGD peptide. Both labeled peptides accumulated in large quantities in the tumor with similar biodistribution, demonstrating their usefulness for radiotheranostics. In this study, we hypothesized that probes for radiotheranostics combined with multiradionuclides, such as 68Ga and 211At, have useful clinical applications. New radiolabeled RGD peptide probes were synthesized via a molecular design approach, with two labeling sites for metal and halogen. These probes were evaluated in biodistribution experiments using tumor-bearing mice. [67Ga]­Ga-DOTA-c­[RGDf­(4-I)­K] ([67Ga]4), Ga-DOTA-[125I]­c­[RGDf­(4-I)­K] ([125I]4), and Ga-DOTA-[211At]­c­[RGDf­(4-At)­K] ([211At]7) showed similar biodistribution, with high and equivalent accumulation in tumors. These results indicate the usefulness of these probes in radiotheranostics with multiradionuclides, such as a radiometal and a radiohalogen, and they could contribute to a personalized medicine regimen.

RGD Peptide-Conjugated Dodecaborate with the Ga-DOTA Complex: A Preliminary Study for the Development of Theranostic Agents for Boron Neutron Capture Therapy and Its Companion Diagnostics

“…In the meantime, the membrane-bound radioactivity [uptake × (1 – internalized ratio)] increased. Although the reason is not apparent, our previous report of radiolabeled RGD peptides showed similar results …”

“…Similarly, previous studies in our and other research groups reported a significantly reduced accumulation in normal tissues by blocking agents (RGD peptides). 28,33,34 The results of the blocking study confirm that [ 67 Ga]16 and [ 125 I]17 are reasonable as α v β 3 integrin-directed radiolabeled RGD peptides because the α v β 3 integrin also expresses on the microvessels of normal tissues, such as the liver and lung. 35 ■…”

“…Cellular uptake experiments were performed according to a previous report with slight modifications. 28 U-87 MG cells were put on 6-well culture plates (7 × 10 5 cells/well) and were cultured for 24 h. After removal of medium, a mixed solution of [ 67 Ga]16 and [ 125 I]17 (11.1 kBq/each tracer/well) in medium without fetal bovine serum was added. After incubation for 1, 3, and 6 h, the medium from each well was removed, and the cells were washed twice with ice-cold EMEM medium.…”

Synthesis and Evaluation of a Dimeric RGD Peptide as a Preliminary Study for Radiotheranostics with Radiohalogens

“…Thus, we synthesized and evaluated the 125/131 I-labeled di- 1) as a preliminary step for radiotheranostics with 211 At-labeled dimer RGD peptide. This is because the radiolabeling with radiohalogens such as 125/131 I and 211 At can be achieved using the same tributyltin precursors, and 125 I-and 211 At-labeled probes showed very similar biodistribution patterns in our previous studies [8,10,11]. Moreover, 125 I is commercially available and has a long half-life (t1/2 = 59.4 d), which is appropriate for fundamental research.…”

“…The binding affinity of 6 for α v β 3 integrin (IC 50 : 1.2 ± 0.5 nM) was higher than that of c[RGDf(4-I)K] (IC 50 : 23.2 ± 17.2 nM) [11]. It was reported that IC 50 values of dimeric RGD peptides in the α v β 3 integrin competitive binding assay were an order lower than those of original monomeric RGD peptides [16].…”