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Data on biodistribution and radiation absorbed dose profile of a novel (64)Cu-labeled high affinity cell-specific peptide for positron emission tomography imaging of tumor vasculature.

ABSTRACT: New peptide-based diagnostic and therapeutic approaches hold promise for highly selective targeting of cancer leading to more precise and effective diagnostic and therapeutic modalities. An important feature of these approaches is to reach the tumor tissue while limiting or minimizing the dose to normal organs. In this context, efforts to design and engineer materials with optimal in vivo targeting and clearance properties are important. This Data In Brief article reports on biodistribution and radiation absorbed dose profile of a novel high affinity radiopeptide specific for bone marrow-derived tumor vasculature. Background information on the design, preparation, and in vivo characterization of this peptide-based targeted radiodiagnostic is described in the article "Synthesis and comparative evaluation of novel 64Cu-labeled high affinity cell-specific peptides for positron emission tomography of tumor vasculature" (Merrill et al., 2016) [1]. Here we report biodistribution measurements in mice and calculate the radiation absorbed doses to normal organs using a modified Medical Internal Radiation Dosimetry (MIRD) methodology that accounts for physical and geometric factors and cross-organ beta doses.

SUBMITTER: Merrill JR

PROVIDER: S-EPMC4792855 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundImmunotherapy is a valuable option for cancer treatment, and the curative effect of anti-PD-1/PD-L1 therapy correlates closely with PD-L1 expression levels. Positron emission tomography (PET) imaging of PD-L1 expression is feasible using 68Ga-NOTA-Nb109 nanobody. 68Ga-NOTA-Nb109 was generated by radionuclide (68Ga) labeling of Nb109 using a NOTA chelator. To facilitate clinical trials, we explored the optimal dose range of 68Ga-NOTA-Nb109 in BALB/c A375-hPD-L1 tumor-burdened nude mice and C57-hPD-L1 transgenic MC38-hPD-L1 tumor-burdened mice by administration of a single intravenous dose of 68Ga-NOTA-Nb109 and confirmed the dose in cynomolgus monkeys. The biodistribution data of cynomolgus monkey PET images were extrapolated to estimate the radiation dose for the adult male and female using OLINDA2.1 software.Results68Ga-NOTA-Nb109 was stable in physiologic media and human serum. Ex vivo biodistribution studies showed rapid and specific uptake in A375-hPD-L1 or MC38-hPD-L1 tumors. The estimated ED50 was approximately 5.4 µg in humanized mice. The injected mass (0.3-100 µg in nude mice and approximately 1-100 µg in humanized mice) greatly influenced the general biodistribution, with a better tumor-to-background ratio acquired at lower doses of Nb109 (0.3-10 µg in nude mice and approximately 1 µg in humanized mice), indicating maximum uptake in tumors at administered mass doses below the estimated ED50. Therefore, a single 15-μg/kg dose was adopted for the PET/CT imaging in the cynomolgus monkey. The highest specific and persistent uptake of the tracer was detected in the spleen, except the levels in the kidney and urine bladder, which was related to metabolism and excretion. The spleen-to-muscle ratio of the tracer exceeded 10 from immediately to 4 h after administration, indicating that the dose was appropriate. The estimated effective dose was calculated to yield a radiation dose of 4.1 mSv to a patient after injecting 185 MBq of 68Ga-NOTA-Nb109.Conclusion68Ga-NOTA-Nb109 showed specific accumulation in hPD-L1 xenografts in ex vivo biodistribution studies and monkey PET/CT imaging. The dose escalation distribution data provided a recommended dose range for further use, and the safety of the tracer was confirmed in dosimetry studies.

Project description:Peptoids are a rapidly developing class of biomimetic polymers based on oligo-N-substituted glycine backbones, designed to mimic peptides and proteins. Inspired by natural antimicrobial peptides, a group of cationic amphipathic peptoids has been successfully discovered with potent, broad-spectrum activity against pathogenic bacteria; however, there are limited studies to address the in vivo pharmacokinetics of the peptoids. Herein, (64)Cu-labeled DOTA conjugates of three different peptoids and two control peptides were synthesized and assayed in vivo by both biodistribution studies and small animal positron emission tomography (PET). The study was designed in a way to assess how structural differences of the peptidomimetics affect in vivo pharmacokinetics. As amphipathic molecules, major uptake of the peptoids occurred in the liver. Increased kidney uptake was observed by deleting one hydrophobic residue in the peptoid, and (64)Cu-3 achieved the highest kidney uptake of all the conjugates tested in this study. In comparison to peptides, our data indicated that peptoids had general in vivo properties of higher tissue accumulation, slower elimination, and higher in vivo stability. Different administration routes (intravenous, intraperitoneal, and oral) were investigated with peptoids. When administered orally, the peptoids showed poor bioavailability, reminiscent of that of peptide. However, remarkably longer passage through the gastrointestinal (GI) tract without rapid digestion was observed for peptoids. These unique in vivo properties of peptoids were rationalized by efficient cellular membrane permeability and protease resistance of peptoids. The results observed in the biodistribution studies could be confirmed by PET imaging, which provides a reliable way to evaluate in vivo pharmacokinetic properties of peptoids noninvasively and in real time. The pharmacokinetic data presented here can provide insight for further development of the antimicrobial peptoids as pharmaceuticals.

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Data on biodistribution and radiation absorbed dose profile of a novel (64)Cu-labeled high affinity cell-specific peptide for positron emission tomography imaging of tumor vasculature.

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