Integrin α_vβ₃ as a Promising Target to Image Neoangiogenesis Using In-House Generator-Produced Positron Emitter ⁶⁸Ga-Labeled DOTA-Arginine-Glycine-Aspartic Acid (RGD) Ligand

Abstract

For the growth and spread of a tumor beyond 2 mm, angiogenesis plays a crucial role, and association of various integrins with angiogenesis is evidential. The aim of the study was radiolabeling of DOTA-chelated RGD (arginine-glycine-aspartic acid) peptide with (68)Ga for PET imaging in locally advanced breast carcinoma. DOTA-RGD was incubated with (68)GaCl3, eluted in 0.05 m HCl. Elution volume, peptide amount, and reaction pH were studied. Radio-ITLC, gas chromatography, endotoxin, and sterility testing were performed. Serial (n=3) and whole-body (n=2) PET/CT imaging was done on patients post i.v. injection of 111-185 MBq of (68)Ga-DOTA-RGD. Maximum radiolabeling yield was achieved with 3 mL elution volume of 15-20 μg peptide at pH 3.5-4.0 with 10 minutes of incubation at 95°C. Product samples were sterile having 99.5% radiochemical purity with residual ethanol content and endotoxins in injectable limits. Intense radiotracer uptake was noticed in the tumor with SUVmax 15.3 at 45 minutes in serial images. Physiological radiotracer uptake was seen in the liver, spleen, ventricles, and thyroid with excretion through the kidneys. The authors concluded that (68)Ga-DOTA-RGD has the potential for imaging α,vβ3 integrin-expressing tumors.

Detailed evaluation of different 68Ge/68Ga generators: an attempt toward achieving efficient 68Ga radiopharmacy

“…Adopting optimized radiolabeling protocol, clinically relevant doses (~370 MBq of 68 Ga) of 68 Ga‐DOTA‐RGD 2 were synthesized using SiO 2 ‐based 68 Ge/ 68 Ga generator (without employing semi‐automated purification module) at Tata Memorial Hospital, Mumbai. For comparison purpose, clinically relevant doses of 68 Ga‐DOTA‐RGD 2 were also synthesized using the same generator coupled to a semi‐automated synthesis module adopting the reported procedure …”

Response Assessment of 68Ga-DOTA-E-[c(RGDfK)]2 PET/CT in Lung Adenocarcinoma Patients Treated with Nintedanib Plus Docetaxel

“…Medical imaging has an advantage as a biomarker by being a noninvasive method that can provide a variety of information about the tumor (24). Integrated PET/CT using 18 F-FDG, the most widespread image radiotracer, can visualize tumor viability, tumor anatomy, and the surrounding normal tissues. The reported sensitivity, specificity, and accuracy of 18 F-FDG PET/CT are 89%, 94%, and 93%, respectively (25).…”

“…The reported sensitivity, specificity, and accuracy of 18 F-FDG PET/CT are 89%, 94%, and 93%, respectively (25). However, it lacks tumor specificity and has poor uptake in tumor-related neovascularization (18,26). Thus, new approaches and optimal imaging methods must be established for new drugs, such as antiangiogenic therapies.…”

“…68 Ga-DOTA-E-[c(RGDfK)] 2 was synthesized according to the method described by López-Rodriguez et al (16) PET/CT Interpretation Criteria 2 PET/CT was performed before the start of treatment and again after 2 cycles of treatment. Negative PET/CT results were defined as tracer confined to normal-uptake organs (spleen, urinary bladder, liver) and no other sites with uptake (16,18). Positive results (progressive disease) were defined as at least one focus of abnormally intense uptake, characterized by visual inspection or SUV max measurements.…”

Preliminary Clinical Application of RGD-Containing Peptides as PET Radiotracers for Imaging Tumors

“…The pharmacokinetics and imaging properties of 18 F-Alfatide were comparable to those of 18 F-FP-PEG3-E[c(RGDyK)]2 (denoted as 18 F-FPPRGD2) (54,70). In addition, the positive effect of cyclic mono or multimeric peptides was also successfully developed into 68 Ga-labeled RGD analogs, which have shown promise for imaging integrin avb3 expression (48,(71)(72)(73)(74)(75)(76)(77)(78)(79).…”