Arg-Gly-Asp (RGD) derivatives have been labeled with various radioisotopes for the imaging of angiogenesis in ischemic tissue, in which α_vβ₃ integrin plays an important role. In this study, cyclic Arg-Gly-Asp-d-Tyr-Lys [c(RGDyK)] was conjugated with 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bz-NOTA) and then labeled with ⁶⁸Ga. The labeled RGD so produced was subjected to an in vitro binding assay and in vivo biodistribution and PET studies. Methods: A mixture of SCN-Bz-NOTA (660 nmol) and c(RGDyK) (600 nmol) in 0.1 M sodium carbonate buffer (pH 9.5) was allowed to react for 20 h at room temperature in the dark for thiourea bond formation. The conjugate obtained was purified by semipreparative high-performance liquid chromatography (HPLC). The purified c(RGDyK)–SCN-Bz-NOTA (NOTA-RGD) was then labeled with ⁶⁸Ga from a ⁶⁸Ge/⁶⁸Ga generator and purified by semipreparative HPLC. A competitive binding assay for c(RGDyK) and NOTA-RGD was performed with ¹²⁵I-c(RGDyK) as a radioligand and α_vβ₃ integrin–coated plates as a solid phase. ⁶⁸Ga-NOTA-RGD (0.222 MBq/100 μL) was injected, through a tail vein, into mice with hind limb ischemia and into mice bearing human colon cancer SNU-C4 xenografts. Biodistribution and imaging studies were performed at 1 and 2 h after injection. Results: The labeling of NOTA-RGD with ⁶⁸Ga was straightforward. The K_i values of c(RGDyK) and NOTA-RGD were 1.3 and 1.9 nM, respectively. In the biodistribution study, the mean ± SD uptake of ⁶⁸Ga-NOTA-RGD by ischemic muscles was 1.6 ± 0.2 percentage injected dose per gram (%ID/g); this uptake was significantly blocked by cold c(RGDyK) to 0.6 ± 0.3 %ID/g (P < 0.01). Tumor uptake was 5.1 ± 1.0 %ID/g, and the tumor-to-blood ratio was 10.3 ± 4.8. Small-animal PET revealed rapid excretion through the urine and high levels of tumor and kidney uptake. Conclusion: Stable ⁶⁸Ga-NOTA-RGD was obtained in a straightforward manner at a high yield and showed a high affinity for α_vβ₃ integrin, specific uptake by angiogenic muscles, a high level of uptake by tumors, and rapid renal excretion. ⁶⁸Ga-NOTA-RGD was found to be a promising radioligand for the imaging of angiogenesis.

A single crystal structure of an aluminium-fluoride complex of a model compound (NODA-benzyl) was studied to understand the co-ordination chemistry. Series of ligands with an extra carboxylic acid linker for biomolecule conjugation were studied for improved ¹⁸F-labeling applications.

We tried to develop a dual-modal PET/MR imaging probe using a straightforward one-pot method by encapsulation with specific amphiphiles. In this study, iron oxide (IO) nanoparticles were encapsulated with three amphiphiles containing PEG, DOTA and the prostate-specific membrane antigen (PSMA)-targeting ligand in aqueous medium. The diameter of the prepared nanoparticle DOTA-IO-GUL was 11.01±1.54nm. DOTA-IO-GUL was labeled with (68)Ga in high efficiency. The DOTA-IO-GUL showed a dose-dependent binding to LNCaP (PSMA positive) cells via a competitive binding study against (125)I-labeled MIP-1072 (PSMA-targeting agent). Additionally, PET and MR imaging results showed PSMA selective uptake by only 22Rv1 (PSMA positive) but not PC-3 (PSMA negative) in dual-tumor xenograft mouse model study. MR imaging showed high resolution, and PET imaging enabled quantification and confirmation of the specificity. In conclusion, we have successfully developed the specific PSMA-targeting IO nanoparticle, DOTA-IO-GUL, as a dual-modality probe for complementary PET/MR imaging. The combination of using Positron Emission Tomography (PET) and computed tomography (CT) in clinical practice is now the norm. With advances in technology, the next step would be to develop combined PET and Magnetic Resonance (MR) dual-imaging. In this article, the authors described their positive study on the development of a dual-modal PET/MR imaging probe using a prostate cancer model.