^99mTc-3P-RGD₂ Micro-Single-Photon Emission Computed Tomography/Computed Tomography Provides a Rational Basis for Integrin α_vβ₃-Targeted Therapy

Abstract

Purpose: This study was to demonstrate the utility of 99m Tc-3P-RGD 2 micro-single-photon emission computed tomography/computed tomography (SPECT/CT) for the integrin a v b 3 expression quantification in NCI-H446 and A549 lung cancer xenografts. Materials and Methods: 99m Tc-3P-RGD 2 was prepared with high radiochemical purity (97% -2%) and showing high in vitro stability. The in vitro affinities of 99m Tc-3P-RGD 2 to NCI-H446 and A549 tumor cells were analyzed with c-counter, while the in vivo uptakes in NCI-H446 and A549 xenografts were evaluated with micro-SPECT/CT. The region of interest was drawn over the tumor site and contralateral muscle on the SPECT/ CT image, and the tumor to nontumor (T/NT) ratio was calculated to estimate a v b 3 expression and tumor uptake. The expressions of integrin a v b 3 in vitro and in vivo were analyzed using a flow cytometer and immunofluorescence. Results: Micro-SPECT/CT demonstrated focal uptake in the tumors. T/NT ratio in NCI-H446 xenografts was significantly higher compared with the A549 tumor model, as 5.92 -0.82 and 3.62 -0.91, respectively, with p < 0.05. In addition, integrin a v b 3 expression in NCI-H446 cells was significantly higher compared with the A549 cells, which was consistent with the imaging data. A linear relationship was observed between 99m Tc-3P-RGD 2 uptake and a v b 3 expression (R 2 = 0.7667, p < 0.001). Conclusion:99m Tc-3P-RGD 2 SPECT/CT could be used to quantify integrin a v b 3 expression within tumors, providing a rational basis for integrin a v b 3 -targeted cancer therapy.

99mTc-3PRGD2 single-photon emission computed tomography/computed tomography for the diagnosis of choroidal melanoma

“…99m Tc-3PRGD2 radiotracer was prepared as described previously. [ 18 ] Briefly, the kit contained 20 μg hydrazinonicotinamide-3PRGD2, 5 mg trisodium triphenylphosphine-3,3′,3′′-trisulfonate, 6.5 mg tricine, 40 mg mannitol, 38.5 mg disodium succinate hexahydrate, and 12.7 mg succinic acid. For 99m Tc radio labeling, 1.0 mL of 1110 to 1480 MBq (30–40 mCi) of Na 99m TcO 4 solution was added to a lyophilized vial.…”

99mTc-Galacto-RGD2 Integrin αvβ3 Targeted Imaging as a Surrogate for Molecular Phenotyping in Lung Cancer: Prospective Study in the Real World

“…Radiolabelled RGD peptide as a target ligand for angiogenesis imaging has been well documented in preclinical and clinical studies [18,26,27]. In a previous multicentre study, we showed that Tc-labelled RGD dimers, such as 99m Tc-3PRGD 2 , had high sensitivity for the detection of lung cancer, including primary and metastatic tumours [26,28,29]. 99m Tc-Galacto-RGD 2 , with higher a nity to α v β 3 and a favourable biodistribution, has been synthesized and utilized for the quantitative evaluation of α v β 3 expression and of tumour angiogenesis, which may in turn serve as a prognostic hallmark and may aid treatment strategy selection [30].…”

[99mTc]Tc-Galacto-RGD2 integrin αvβ3-targeted imaging as a surrogate for molecular phenotyping in lung cancer: real-world data

“…Radiolabelled RGD peptide as a target ligand for angiogenesis imaging has been well documented in preclinical and clinical studies [ 12 , 21 , 22 ]. In a previous multicentre study, we showed that [ 99m Tc]Tc labelled RGD dimers, such as [ 99m Tc]Tc-3PRGD 2 , had high sensitivity for the detection of lung cancer, including primary and metastatic tumours [ 21 , 23 , 24 ] . [ 99m Tc]Tc-Galacto-RGD 2 , with higher affinity to α v β 3 and a favourable biodistribution, has been synthesized and utilized for the quantitative evaluation of α v β 3 expression and of tumour angiogenesis [ 25 ].…”