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• W2907090702 abstract "Human tumors show intrinsic heterogeneity and changes in phenotype during disease progression, which implies different expression levels of cell surface receptors. The research on new heterodimeric lutetium-177 (Lu)-radiopharmaceuticals interacting with two different targets on tumor cells is a strategy for improvement of radiotheranostic performance. This study aimed to synthesize and characterize the Lu-DOTA-PSMA(inhibitor)-Lys-bombesin (Lu-DOTA-iPSMA-Lys-BN) heterodimer and to evaluate its potential to target prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPr) overexpressed in prostate cancer.The heterodimeric conjugate was synthesized and characterized by infrarred, mass, and H-NMR spectroscopies. The ligand was labeled with Lu and the radiochemical purity was assessed by radio-high-performance liquid chromatography. PSMA/GRPr affinity and the heterobivalent effect on cell viability were evaluated in LNCaP and PC3 prostate cancer cell lines. The biodistribution profile (3 and 96 h) was assessed in athymic mice with induced prostate tumors. Using pulmonary LNCaP (PSMA-positive) and PC3 (GRPr-negative) micrometastasis models, the influence of heterobivalency and affinity on tumor uptake was quantified (micro-SPECT/CT).Lu-iPSMA-BN (radiochemical purity>98%) showed specific recognition for PSMA and GRPr (IC50=5.62 and 3.49 nmol/l, respectively) with a significant decrease in cell viability (10.15% of cell viability in LNCaP and 40.10% in PC3 at 48 h), as well as high LNCaP and PC3 tumor uptake (5.21 and 3.21% ID/g at 96 h, respectively). Micro-SPECT/CT imaging showed the heterodimer ability to target the tumors (SUVmax of 1.93±0.30 and 1.76±0.10 in LNCaP and PC3, respectively), possibly influenced by the heterobivalent effect. Lu-DOTA-iPSMA-Lys-BN showed suitable affinity for PSMA and GRPr.The results warrant further preclinical studies to establish the Lu-radiotracer theranostic efficacy." @default.
• W2907090702 created "2019-01-11" @default.
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• W2907090702 date "2019-03-01" @default.
• W2907090702 modified "2023-10-16" @default.
• W2907090702 title "Synthesis and preclinical evaluation of the 177Lu-DOTA-PSMA(inhibitor)-Lys3-bombesin heterodimer designed as a radiotheranostic probe for prostate cancer" @default.
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• W2907090702 doi "https://doi.org/10.1097/mnm.0000000000000966" @default.
• W2907090702 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30763290" @default.
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