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Preparing a <sup>68</sup>Ga-labeled Arginine Glycine Aspartate (RGD)-peptide for Angiogenesis

The &#945;v&#946;3 integrin is a heterodimeric adhesion molecule involved in tumor cell migration and angiogenesis. The integrin is overexpressed in ...

Korea Institute of Radiological and Medical Sciences

Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images. 

Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide.

To develop a radioactive metal complex platform for tumor theranostics, we introduced three radiopharmaceutical derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid-benzothiazole aniline (DO3A-BTA, L1) labeled with medical radioisotopes for diagnosis (Ga/Cu) and therapy (Lu). The tumor-targeting ability of these complexes was demonstrated in a cellular uptake experiment, in which Lu-L1 exhibited markedly higher uptake in HeLa cells than the Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex. According to in vivo positron emission tomography imaging, high accumulation of Ga-L1 and Cu-L1 was clearly visualized in the tumor site, while Lu-L1 showed therapeutic efficacy in therapy experiments. Consequently, this molecular platform represents a useful approach in nuclear medicine toward tumor-theranostic radiopharmaceuticals when Ga-L1 or Cu-L1 is used for diagnosis, Lu-L1 is used for therapy, or two of the compounds are used in conjunction with each other.

Radiometallic Complexes of DO3A-Benzothiazole Aniline for Nuclear Medicine Theranostics.

Epidermal growth factor receptor (EGFR) is overexpressed and considered as a proper molecular target for diagnosis and targeted therapy of esophageal squamous cell carcinoma (ESCC). This study evaluated the usefulness of PET imaging biomarkers with Cu-PCTA-cetuximab and F-FDG-PET for anti-EGFR immunotherapy in ESCC models.  EGFR status and glucose metabolism by cetuximab treatment were evaluated using Cu-PCTA-cetuximab and F-FDG-PET, respectively. Therapeutic responses with imaging biomarkers were confirmed by western blot and immunohistochemistry. TE-4 and TE-8 tumors were clearly visualized by Cu-PCTA-cetuximab, and EGFR expression on TE-8 tumors showed 2.6-fold higher uptake than TE-4. Tumor volumes were markedly reduced by cetuximab in TE-8 tumor (92.5 ± 5.9%), but TE-4 tumors were refractory to cetuximab treatment. The SUVs in Cu-PCTA-cetuximab and F-FDG-PET images were statistically significantly reduced by cetuximab treatment in TE-8 but not in TE-4. Cu-PCTA-cetuximab and F-FDG-PET images were well correlated with EGFR and pAkt levels. Cu-PCTA-cetuximab immuno-PET had a potential for determining EGFR level and monitoring therapeutic response by anti-EGFR therapy. F-FDG-PET was also attractive for monitoring efficacy of anti-EGFR therapy. In conclusion, PET imaging biomarkers may be useful for selecting patients that express target molecules and for monitoring therapeutic efficacy of EGFR-targeted therapy in ESCC patients.

Article	Year
Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide. Biochemical and biophysical research communications\| PubMed ID: 25449282	2014
Radiometallic Complexes of DO3A-Benzothiazole Aniline for Nuclear Medicine Theranostics. Molecular pharmaceutics\| PubMed ID: 29381860	2018
PET Imaging Biomarkers of Anti-EGFR Immunotherapy in Esophageal Squamous Cell Carcinoma Models. Cells\| PubMed ID: 30373221	2018

Jung Young Kim

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