Comparative Evaluation of 68Ga-labeled NODAGA, DOTAGA and HBED-CC conjugated cNGR Peptide Chelates as Tumor Targeted Molecular Imaging Probes

Abstract

The biological behavior of ⁶⁸Ga-based radiopharmaceuticals can be significantly affected by the chelators' attributes (size, charge, lipophilicity). Thus this study aimed at examining the influence of three different chelators, DOTAGA, NODAGA and HBED-CC on the distribution pattern of ⁶⁸Ga-labeled NGR peptides targeting CD13 receptors. ⁶⁸Ga-DOTAGA-c(NGR), ⁶⁸Ga-NODAGA-c(NGR) and ⁶⁸Ga-HBED-CC-c(NGR) were observed to be hydrophilic with respective log P values being -3.5±0.2, –3.3±0.08 and -2.8±0.14. The three radiotracers exhibited nearly similar uptake in human fibrosarcoma HT-1080 tumor cells with 86, 63 and 33% reduction during blocking studies with unlabeled cNGR peptide for ⁶⁸Ga-DOTAGA-c(NGR), ⁶⁸Ga-NODAGA-c(NGR) and ⁶⁸Ga-HBED-CC-c(NGR) respectively indicating higher receptor specificity of the first two radiotracers. The neutral radiotracer ⁶⁸Ga-NODAGA-c(NGR) demonstrated better target-to-non-target ratios during in vivo studies compared to its negatively charged counterparts, ⁶⁸Ga-DOTAGA-c(NGR) and ⁶⁸Ga-HBED-CC-c(NGR). The three radiotracers had similar HT-1080 tumor uptake and being hydrophilic exhibited renal excretion with minimal uptake in non-target organs. Significant reduction (p<0.005) in HT-1080 tumor uptake of the radiotracers was observed during blocking studies. It may be inferred from these studies that the three radiotracers are promising probes for in vivo imaging of CD13 receptor expressing cancer sites however ⁶⁸Ga-NODAGA-c(NGR) is a better candidate.

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The goal of this study was to determine the influence of three different chelators, DOTAGA, NODAGA and HBED-CC on pharmacokinetics and biodistribution pattern of ⁶⁸Ga-labeled NGR peptides targeting CD13 receptors.

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