Comparative evaluation of 68Ga‐labeled NODAGA, DOTAGA, and HBED‐CC‐conjugated cNGR peptide chelates as tumor‐targeted molecular imaging probes

The biological behavior of 68 Ga‐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 68 Ga‐labeled NGR peptides targeting CD 13 receptors. 68 Ga‐ DOTAGA ‐c( NGR ), 68 Ga‐ NODAGA ‐c( NGR ), and 68 Ga‐ 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 68 Ga‐ DOTAGA ‐c( NGR ), 68 Ga‐ NODAGA ‐c( NGR ), and 68 Ga‐ HBED ‐ CC ‐c( NGR ), respectively, indicating higher receptor specificity of the first two radiotracers. The neutral radiotracer 68 Ga‐ NODAGA ‐c( NGR ) demonstrated better target‐to‐non‐target ratios during in vivo studies compared to its negatively charged counterparts, 68 Ga‐ DOTAGA ‐c( NGR ) and 68 Ga‐ 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 < .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 CD 13 receptor expressing cancer sites; however, 68 Ga‐ NODAGA ‐c( NGR ) is a better candidate.