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. 2016 Feb;31(1):29-36.
doi: 10.1089/cbr.2015.1947.

Evaluation of a PACAP Peptide Analogue Labeled with (68)Ga Using Two Different Chelating Agents

Pardeep Kumar  1 , Sushil Kumar Tripathi  1 , Chang-Po Chen  2 , Neil Mehta  1 , Bishnuhari Paudyal  1 , Eric Wickstrom  3   4 , Mathew L Thakur  1   4   5
Affiliations

Evaluation of a PACAP Peptide Analogue Labeled with (68)Ga Using Two Different Chelating Agents

Pardeep Kumar et al. Cancer Biother Radiopharm. 2016 Feb.

Abstract

Objective: The authors have conjugated chelating agents (DOTA and NODAGA) with a peptide (pituitary adenylate cyclase-activating peptide [PACAP] analogue) that has a high affinity for VPAC1 receptors expressed on cancer cells. To determine a suitable chelating agent for labeling with (68)Ga, they have compared the labeling kinetics and stability of these peptide conjugates.

Methods: For labeling, (68)GaCl3 was eluted in 0.1 M HCl from a [(68)Ge-(68)Ga] generator. The influences of peptide concentration, pH, and temperature on the radiolabeling efficiency were studied. The stability was evaluated in saline, human serum, DTPA, transferrin, and metallic ions (FeCl3, CaCl2, and ZnCl2). Cell binding assay was performed using human breast cancer cells (T47D). Tissue biodistribution was studied in normal athymic nude mice.

Results: Optimal radiolabeling (>95.0%) of the DOTA-peptide conjugates required a higher (50°C-90°C) temperature and 10 minutes of incubation at pH 2-5. The NODAGA-peptide conjugate needed incubation only at 25°C for 10 minutes. Both radiocomplexes were stable in saline, serum, as well as against transchelation and transmetallation. Cell binding at 37°C for 15 minutes of incubation with (68)Ga-NODAGA-peptide was 34.0% compared to 24.5% for (68)Ga-DOTA-peptide. Tissue biodistribution at 1 hour postinjection of both (68)Ga-labeled peptide conjugates showed clearance through the kidneys.

Conclusions: NODAGA-peptide showed more convenient radiolabeling features than that of DOTA-peptide.

Keywords: breast cancer; chelating agent; peptides; prostate cancer; radiopharmaceuticals.

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Figures

<b>FIG. 1.</b>
FIG. 1.
Mass spectrometry of (A) NODAGA-peptide (TP-3718) and (B) DOTA-peptide conjugates (TP-3785).
<b>FIG. 2.</b>
FIG. 2.
Influence of temperature and pH on (A) 68Ga-NODAGA-peptide and (B) 68Ga-DOTA-peptide. (C) Influence of peptide concentration on labeling efficiency. (D) Influence of incubation time on labeling efficiency on 68Ga-NODAGA- and DOTA-peptide conjugate.
<b>FIG. 3.</b>
FIG. 3.
(A) Schematic diagram of radiolabeling of NODAGA-peptide with 68Ga. (B) Radio-high-pressure liquid chromatography showing retention time for 68Ga-NODAGA-peptide conjugate at 9.9 minutes and for free 68GaCl3 at 3.6 minutes (slope indicates the solvent gradient).
<b>FIG. 4.</b>
FIG. 4.
Stability in (A) normal saline, (B) ferric chloride, (C) calcium chloride, and (D) zinc chloride.
<b>FIG. 5.</b>
FIG. 5.
Transchelation study with (A) DTPA solution and (B) transferrin solution.
<b>FIG. 6.</b>
FIG. 6.
Tissue biodistribution of 68Ga-NODAGA-peptide (n = 5) and 68Ga-DOTA-peptide conjugate (n = 5) at 1 hour.
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