Preclinical Evaluation of a Fluorine-18 Labeled Probe for the Detection of the Expression of PSMA Level in Cancer

Abstract

Prostate-specific membrane antigen (PSMA) is a prospect biomarker for the treatment of prostate cancer. Meanwhile, positron emission tomography (PET) is being developed as a significant imaging modality in cancer diagnosis. A new PET probe Glu-ureido-Lysnaphthylalanine-tranexamic acid-Gly(AMBF 3 )-triiodobenzoic acid ( 18 F-GLNTGT) was radiosynthesized by a one-step 18 F-labeled method. 18 F-GLNTGT was obtained with a radioactivity yield (RCY) of 12.16 ± 6.4% and a good radiochemical purity (RCP > 96%). The cell uptakes of 18 F-GLNTGT were determined to be 15.9 ± 0.43% ID and 9.47 ± 1.26% ID at 15 min in LNCaP cells and PC-3 cells, respectively. The cell internalization of 18 F-GLNTGT was determined to be 12.89 ± 0.94% ID and 5.34 ± 0.15% ID at 15 min in LNCaP cells and PC-3 cells, respectively. It is suggested that the probe has good specificity targeting PSMA. From the results of 18 F-GLNTGT binding affinity with PSMA, it has a higher affinity and a K i value of 0.49 nM (95% confidence interval (CI): 0.35−0.67 nM). In PET imaging, 18 F-GLNTGT showed the highest tumor uptake of 3.51 ± 0.15% ID/g at 45 min and the maximum tumor/muscle (T/M max ) ratio of 3.68 ± 0.29 at 60 min post-injection (p.i.) in LNCaP tumors. The control probe 18 F-AlF-NOTA-RGD 2 presented the highest tumor uptake of 4.2 ± 0.54% ID/g at 7.5 min and the T/M max ratio of 2.72 ± 0.63 at 45 min p.i. in LNCaP tumors. The results showed that the probe has a higher tumor/muscle ratio compared with the control probe 18 F-AlF-NOTA-RGD 2 . Although the probe 18 F-GLNTGT has some limitations for CT signal detection both in cells and in vivo, it is still a promising PET probe for targeting PSMA membrane protein.

Cyanopyridoimidazole/1,2-Aminothiol Click Reaction: A Novel Bioorthogonal Reaction for Synthesis of Radiotracers

“…As shown in Scheme , upon the condensation of 14 and a Cys-modified PSMA-617 ( S14 ), followed by labeling with radioactive [ 67 Ga]­GaCl 3 , we obtained [ 67 Ga]­Ga- 15 in a radiochemical yield (RCY) of 99% with a molar activity of 4.6 MBq/nmol (Figure S7). The log D 7.4 of [ 67 Ga]­Ga- 15 was measured as −2.11 ± 0.07, which was within the normal range of other reported radiolabeled PSMA-617. − …”

Recent Advances in Bioorthogonal Click Chemistry for Enhanced PET and SPECT Radiochemistry

“…Lin and co-workers recently demonstrated a comparable method for the manufacture of a GGT-targeting peptide probe with a high RCP (>98%) and a high molar activity (10.64 ± 0.89 GBq/μmol) by adding an AmBF 3 -modified azide moiety to the peptide targeting γ-glutamyltranspeptidase (GGT) . Subsequently, the same group radiolabeled a prostate-specific membrane antigen (PSMA)-targeted peptide ligand to generate a specific PET probe with a higher tumor-to-muscle ratio than the control probe [ 18 F]­AlF-NOTA-RGD2 (NOTA: 1,4,7-triazacyclononane-1,4,7-triacetic acid) . Melanocortin 1 receptor (MC1R)-targeted peptides were radiolabeled using identical 18 F-labeling techniques to produce [ 18 F]­CCZ01064 and [ 18 F]­CCZ01096 with a high radiochemical purity (>95%) and good molar activity (40.7–66.6 MBq/nmol and 115.5–266.5 MBq/nmol, respectively), for imaging melanoma. , Iannone et al group used the CuAAC reaction for 18 F-labeling of a PSMA-617 peptide-based precursor.…”