Development of a potential gallium-68-labelled radiotracer based on DOTA-curcumin for colon-rectal carcinoma: From synthesis to in vivo studies

Giulia Orteca, Federica Pisaneschi, Sara Rubagotti, Tracy W. Liu, Giacomo Biagiotti, David Piwnica-Worms, Michele Iori, Pier Cesare Capponi, Erika Ferrari, Mattia Asti

Research output: Contribution to journalArticle

Abstract

Colorectal cancer is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women worldwide. We have recently reported that curcuminoid complexes labelled with gallium-68 have demonstrated preferential uptake in HT29 colorectal cancer and K562 lymphoma cell lines compared to normal human lymphocytes. In the present study, we report a new gallium-68-labelled curcumin derivative ( 68 Ga-DOTA-C21) and its initial validation as marker for early detection of colorectal cancer. The precursor and non-radioactive complexes were synthesized and deeply characterized by analytical methods then the curcuminoid was radiolabelled with gallium-68. The in vitro stability, cell uptake, internalization and efflux properties of the probe were studied in HT29 cells, and the in vivo targeting ability and biodistribution were investigated in mice bearing HT29 subcutaneous tumour model. 68 Ga-DOTA-C21 exhibits decent stability (57 ± 3% after 120 min of incubation) in physiological media and a curcumin-mediated cellular accumulation in colorectal cancer cell line (121 ± 4 KBq of radiotracer per mg of protein within 60 min of incubation). In HT29 tumour-bearing mice, the tumour uptake of 68 Ga-DOTA-C21 is 3.57 ± 0.3% of the injected dose per gram of tissue after 90 min post injection with a tumour to muscle ratio of 2.2 ± 0.2. High amount of activity (12.73 ± 1.9% ID/g) is recorded in blood and significant uptake of the radiotracer occurs in the intestine (13.56 ± 3.3% ID/g), lungs (8.42 ± 0.8% ID/g), liver (5.81 ± 0.5% ID/g) and heart (4.70 ± 0.4% ID/g). Further studies are needed to understand the mechanism of accumulation and clearance; however, 68 Ga-DOTA-C21 provides a productive base-structure to develop further radiotracers for imaging of colorectal cancer.

Original languageEnglish
JournalMolecules
Volume24
Issue number3
DOIs
Publication statusPublished - Feb 12 2019

Fingerprint

Gallium
Curcumin
gallium
Tumors
Colon
Bearings (structural)
cancer
Colorectal Neoplasms
Carcinoma
synthesis
tumors
Neoplasms
Cells
Lymphocytes
cultured cells
mice
Liver
Muscle
Cell Line
HT29 Cells

Keywords

  • Colorectal cancer
  • Curcuminoids
  • Gallium-68
  • Positron emission tomography
  • Radiotracers

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Development of a potential gallium-68-labelled radiotracer based on DOTA-curcumin for colon-rectal carcinoma : From synthesis to in vivo studies. / Orteca, Giulia; Pisaneschi, Federica; Rubagotti, Sara; Liu, Tracy W.; Biagiotti, Giacomo; Piwnica-Worms, David; Iori, Michele; Capponi, Pier Cesare; Ferrari, Erika; Asti, Mattia.

In: Molecules, Vol. 24, No. 3, 12.02.2019.

Research output: Contribution to journalArticle

Orteca, Giulia ; Pisaneschi, Federica ; Rubagotti, Sara ; Liu, Tracy W. ; Biagiotti, Giacomo ; Piwnica-Worms, David ; Iori, Michele ; Capponi, Pier Cesare ; Ferrari, Erika ; Asti, Mattia. / Development of a potential gallium-68-labelled radiotracer based on DOTA-curcumin for colon-rectal carcinoma : From synthesis to in vivo studies. In: Molecules. 2019 ; Vol. 24, No. 3.
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abstract = "Colorectal cancer is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women worldwide. We have recently reported that curcuminoid complexes labelled with gallium-68 have demonstrated preferential uptake in HT29 colorectal cancer and K562 lymphoma cell lines compared to normal human lymphocytes. In the present study, we report a new gallium-68-labelled curcumin derivative ( 68 Ga-DOTA-C21) and its initial validation as marker for early detection of colorectal cancer. The precursor and non-radioactive complexes were synthesized and deeply characterized by analytical methods then the curcuminoid was radiolabelled with gallium-68. The in vitro stability, cell uptake, internalization and efflux properties of the probe were studied in HT29 cells, and the in vivo targeting ability and biodistribution were investigated in mice bearing HT29 subcutaneous tumour model. 68 Ga-DOTA-C21 exhibits decent stability (57 ± 3{\%} after 120 min of incubation) in physiological media and a curcumin-mediated cellular accumulation in colorectal cancer cell line (121 ± 4 KBq of radiotracer per mg of protein within 60 min of incubation). In HT29 tumour-bearing mice, the tumour uptake of 68 Ga-DOTA-C21 is 3.57 ± 0.3{\%} of the injected dose per gram of tissue after 90 min post injection with a tumour to muscle ratio of 2.2 ± 0.2. High amount of activity (12.73 ± 1.9{\%} ID/g) is recorded in blood and significant uptake of the radiotracer occurs in the intestine (13.56 ± 3.3{\%} ID/g), lungs (8.42 ± 0.8{\%} ID/g), liver (5.81 ± 0.5{\%} ID/g) and heart (4.70 ± 0.4{\%} ID/g). Further studies are needed to understand the mechanism of accumulation and clearance; however, 68 Ga-DOTA-C21 provides a productive base-structure to develop further radiotracers for imaging of colorectal cancer.",
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