Abstract
The α(v)β₃ integrin is highly expressed in prostate cancer (PCa), in which it is a key player in tumour invasion, angiogenesis and metastasis formation. Therefore, α(v)β₃ integrin is considered a very promising target for molecular imaging of PCa. This study tested the potential of the novel α(v)β₃ integrin affine agent [⁶⁸Ga]NOTA-RGD in comparison with the established [¹⁸F]fluoroethylcholine (FEC) and [¹⁸F]fluorodeoxyglucose (FDG) for assessing PCa using positron emission tomography (PET). [⁶⁸Ga]NOTA-RGD showed a lower uptake in PC-3 and DU-145 cells compared with FEC and FDG. µPET imaging studies showed a good delineation of the PCa xenografts in mice. The means tumor-to-muscle and tumor-to-bone-ratio amounted 5.1 ± 1.4 and 5.2 ± 1.2 for [⁶⁸Ga]NOTA-RGD compared with 2.6 ± 0.9 and 2.9 ± 1.6 for FDG, and 2.4 ± 0.7 and 0.8 ± 0.2 for FEC, respectively. The uptake of [⁶⁸Ga]NOTA-RGD into tumor was fully inhibited by c(RGDfV), known to bind specifically to α(v)β₃ integrin, confirming the specificity of the tumor uptake in vivo. These results suggest that [⁶⁸Ga]NOTA-RGD is a promising candidate for PET imaging of α(v)β₃ integrin expression in PCa and warrant further in vivo validations to ascertain its potential as an imaging agent for clinical use. The simple and fast preparation of [⁶⁸Ga]NOTA-RGD may greatly facilitate its translation to a clinical setting.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Affinity Labels* / chemistry
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Affinity Labels* / metabolism
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Animals
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Biological Transport / drug effects
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Cell Line, Tumor
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Choline / analogs & derivatives
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Choline / metabolism
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Coordination Complexes* / antagonists & inhibitors
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Coordination Complexes* / metabolism
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Fluorodeoxyglucose F18 / metabolism
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Gallium Radioisotopes* / chemistry
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Gallium Radioisotopes* / metabolism
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Humans
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Integrin alphaV / chemistry
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Integrin alphaV / metabolism*
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Integrin beta3 / chemistry
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Integrin beta3 / metabolism*
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Integrins / antagonists & inhibitors
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Integrins / metabolism
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Isotope Labeling
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Male
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Mice, Nude
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / metabolism
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Neoplasm Transplantation
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Oligopeptides* / antagonists & inhibitors
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Oligopeptides* / metabolism
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Peptides, Cyclic / administration & dosage
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Peptides, Cyclic / pharmacology
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Positron-Emission Tomography
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Prostate / diagnostic imaging*
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Prostate / drug effects
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Prostate / metabolism
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Prostate / pathology
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Prostatic Neoplasms / diagnostic imaging*
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Radiopharmaceuticals / chemistry
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Radiopharmaceuticals / metabolism
Substances
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68Ga-1,4,7-triazacyclononane-1,4-7-triacetic acid-isothiocyanatobenzyl-c(Arg-Gly-Asp-Tyr-Lys)
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Affinity Labels
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Coordination Complexes
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Gallium Radioisotopes
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Integrin alphaV
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Integrin beta3
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Integrins
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Neoplasm Proteins
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Oligopeptides
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Peptides, Cyclic
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Radiopharmaceuticals
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cyclo(arginyl-glycyl-aspartyl-phenylalanyl-valyl)
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Fluorodeoxyglucose F18
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fluoroethylcholine
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Choline