PET Imaging of the Neurotensin Targeting Peptide NOTA-NT-20.3 Using Cobalt-55, Copper-64 and Gallium-68

Houson, Hailey A.; Tekin, Volkan; Lin, Wilson; Aluicio-Sarduy, Eduardo; Engle, Jonathan W.; Lapi, Suzanne E.

doi:10.3390/pharmaceutics14122724

PET Imaging of the Neurotensin Targeting Peptide NOTA-NT-20.3 Using Cobalt-55, Copper-64 and Gallium-68

Journal Article · Tue Dec 06 00:00:00 EST 2022 · Pharmaceutics

DOI:https://doi.org/10.3390/pharmaceutics14122724· OSTI ID:2421869

Houson, Hailey A. ^[1]; Tekin, Volkan ^[2]; ^[3]; ^[3]; ^[3]; ^[2]

Univ. of Alabama, Birmingham, AL (United States); Univ. of Alabama, Birmingham, AL (United States)
Univ. of Alabama, Birmingham, AL (United States)
Univ. of Wisconsin, Madison, WI (United States)

Introduction: Neurotensin receptor 1 (NTSR1) is an emerging target for imaging and therapy of many types of cancer. Nuclear imaging of NTSR1 allows for noninvasive assessment of the receptor levels of NTSR1 on the primary tumor, as well as potential metastases. This work focuses on a the neurotensin peptide analogue NT-20.3 conjugated to the chelator NOTA for radiolabeling for use in noninvasive positron emission tomography (PET). NOTA-NT-20.3 was radiolabeled with gallium-68, copper-64, and cobalt-55 to determine the effect that modification of the radiometal has on imaging and potential therapeutic properties of NOTA-NT-20.3. Methods: In vitro assays investigating cell uptake and subcellular localization of the radiolabeled peptides were performed using human colorectal adenocarcinoma HT29 cells. In vivo PET/CT imaging was used to determine the distribution and clearance of the peptide in mice bearing NTSR1 expressing HT29 tumors. Results: Cell uptake studies showed that the highest uptake was obtained with [⁵⁵Co] Co-NOTA-NT-20.3 (18.70 ± 1.30%ID/mg), followed by [⁶⁴Cu] Cu-NOTA-NT-20.3 (15.46 ± 0.91%ID/mg), and lastly [⁶⁸Ga] Ga-NOTA-NT-20.3 (10.94 ± 0.46%ID/mg) (p < 0.001). Subcellular distribution was similar across the three constructs, with the membranous fraction containing the highest amount of radioactivity. In vivo PET/CT imaging of the three constructs revealed similar distribution and tumor uptake at the 1 h imaging timepoint. Tumor uptake was receptor-specific and blockable by co-injection of non-radiolabeled NOTA-NT-20.3. SUV ratios of tumor to heart at the 24 h imaging timepoint show that [⁵⁵Co] Co-NOTA-NT-20.3 (20.28 ± 3.04) outperformed [⁶⁴Cu] Cu-NOTA-NT-20.3 (6.52 ± 1.97). In conclusion, our studies show that enhanced cell uptake and increasing tumor to blood ratios over time displayed the superiority of [⁵⁵Co] Co-NOTA-NT-20.3 over [⁶⁸Ga] Ga-NOTA-NT-20.3 and [⁶⁴Cu] Cu-NOTA-NT-20.3 for the targeting of NTSR1.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Alabama, Birmingham, AL (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0021269

OSTI ID:: 2421869

Journal Information:: Pharmaceutics, Journal Name: Pharmaceutics Journal Issue: 12 Vol. 14; ISSN 1999-4923

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
Cobalt-55
Copper-64
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Neurotensin
PET
Pharmacology & Pharmacy

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