Evaluation of a Flexible NOTA-RGD Kit Solution Using Gallium-68 from Different 68Ge/68Ga-Generators: Pharmacokinetics and Biodistribution in Nonhuman Primates and Demonstration of Solitary Pulmonary Nodule Imaging in Humans

Ebenhan, Thomas; Schoeman, Isabel; Rossouw, Daniel D.; Grobler, Anne; Marjanovic-Painter, Biljana; Wagener, Judith; Kruger, Hendrik G.; Sathekge, Mike; Zeevaart, Jan Rijn

doi:10.1007/s11307-016-1014-1

Cited by 14 publications

(10 citation statements)

References 65 publications

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“…Ethical approval was given by the Pretoria University (H001-09). The Biomedical Research Centre (Onderstepoort, Pretoria University) provided and handled the NHPs as previously described (27).…”

Section: Ga-nota-ubi Pharmacokinetics and Tracer Biodistribution In Nhpsmentioning

confidence: 99%

⁶⁸Ga-NOTA-Functionalized Ubiquicidin: Cytotoxicity, Biodistribution, Radiation Dosimetry, and First-in-Human PET/CT Imaging of Infections

et al. 2017

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Ubiquicidin is an antimicrobial peptide with great potential for nuclear imaging of infectious diseases, as its cationic-rich fragment TGRAKRRMQYNRR (UBI) has been functionalized with NOTA to allow complexation to Ga (Ga-NOTA-UBI). We herein assess the cytotoxicity and radiation dosimetry for Ga-NOTA-UBI and a first-in-human evaluation to diagnose infectious processes. Cytotoxicity was evaluated in green monkey kidney epithelial (Vero) cells and MT-4 leukocytes. Tracer susceptibility was studied in vitro using different bacterial and fungal strains. PET/CT-based biodistribution, pharmacokinetics, and radiation dosimetry were performed on nonhuman primates. Two healthy volunteers and 3 patients with suspected infection underwent Ga-NOTA-UBI PET/CT imaging. Negligible cytotoxicity was determined for NOTA-UBI. Ga-NOTA-UBI showed moderate blood clearance (29-min half-life) and predominant renal clearance in nonhuman primates. Human radiation dose estimates indicated the bladder wall as the dose-critical tissue (185 μSv/MBq), followed by the kidneys (23 μSv/MBq). The total absorbed body dose was low (<7 μSv/MBq); the effective dose was estimated at 17 μSv/MBq. Ga-NOTA-UBI could diagnose bone- and soft-tissue infection in 3 of 3 patients.Ga-NOTA-UBI is considered a nontoxic, safe-to-administer radiopharmaceutical unlikely to cause adverse effects in humans. The favorable tracer biodistribution and the first-in-human results will make Ga-NOTA-UBI PET/CT an encouraging future diagnostic technique with auxiliary clinical relevance.

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Section: Ga-nota-ubi Pharmacokinetics and Tracer Biodistribution In Nhpsmentioning

confidence: 99%

⁶⁸Ga-NOTA-Functionalized Ubiquicidin: Cytotoxicity, Biodistribution, Radiation Dosimetry, and First-in-Human PET/CT Imaging of Infections

et al. 2017

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“…When compared with other previously reported tracers targeting c-Met (e.g., 18.1 6 4.5 %ID/g for 89 Zr-DN30 in GTL-16 gastric cancer and 3.4 6 0.3 %ID/g for 89 Zr-DFO-H2cys-diabody in Hcc827-GR NSCLC when there is optimal image contrast) (14,15), the smaller 99m Tc-HYNIC-cMBP showed moderate uptake (4.74 6 1.43 %ID/g). However, H1993 tumors were clearly visualized in SPECT images at as early as 0.5 h. Additionally, 99m Tc-HYNIC-cMBP cleared rapidly via the renal system, as is consistent with water-soluble low-molecular-weight probes, albeit unattractive for imaging tumors of the urinary system (32,33). Nevertheless, rapid clearance is a desirable property for diagnostic tracers, as it reduces tissue exposure to radiation, background noise, and long delays between contrast treatment and image readout for receptortargeted imaging.…”

Section: Discussionmentioning

confidence: 53%

Development of a SPECT Tracer to Image c-Met Expression in a Xenograft Model of Non–Small Cell Lung Cancer

et al. 2018

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Elevated expression of the c-Met receptor plays a crucial role in cancers. In non-small cell lung cancer (NSCLC), aberrant activation of the c-Met signaling pathway contributes to tumorigenesis and cancer progression and may mediate acquired resistance to epidermal growth factor receptor-targeted therapy. c-Met is therefore emerging as a promising therapeutic target for NSCLC, and methods for noninvasive in vivo assessment of c-Met expression would improve NSCLC treatment and diagnosis. We developed a new c-Met-binding peptide (cMBP) radiotracer,Tc-hydrazine nicotinamide (HYNIC)-cMBP, for SPECT imaging. Cell uptake assays were performed on 2 NSCLC cell lines with different c-Met expressions: H1993 (high expression) and H1299 (no expression). In vivo tumor specificity was assessed by SPECT imaging in tumor-bearing mice at 0.5, 1, 2, and 4 h after injection of the probe. Blocking assays, biodistribution, and autoradiography were also conducted to determine probe specificity. Tc-HYNIC-cMBP was prepared with high efficiency and showed higher uptake in H1993 cells than in H1299 cells. Biodistribution and autoradiography also showed significantly higher percentages of the injected dose forTc-HYNIC-cMBP in H1993 tumors than in H1299 tumors at 0.5 h (4.74 ± 1.43%/g and 1.00 ± 0.37%/g, respectively; < 0.05). H1993 tumors were clearly visualized at 0.5 h in SPECT images, whereas H1299 tumors were not observed at any time. The specificity of Tc-HYNIC-cMBP for c-Met was demonstrated by a competitive block with an excess of nonradiolabeled peptide. For c-Met-targeted SPECT imaging of NSCLC, we developed Tc-HYNIC-cMBP, a tracer that specifically binds to c-Met with favorable pharmacokinetics in vitro and in vivo.

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“…RGD was also conjugated with NOTA to make a ligand NOTA‐RGD. Then 18 FAl, 64 Cu, and 68 Ga labeled NOTA‐RGD were further prepared as tumor‐targeting tracers and successfully applied to PET imaging the angiogenesis in animal …”

Section: Introductionmentioning

confidence: 99%

Al¹⁸F labeled sulfonamide‐conjugated positron emission tomography tracer in vivo tumor‐targeted imaging

Liu

Zhao

Xia

et al. 2019

J of Cellular Biochemistry

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An ideal positron emission tomography (PET) tracer should be highly extractable by the tumor tissue or organ that contains low toxicity and can provide high‐resolution images in vivo. In this work, the aim was to evaluate the application of Al18F‐labeled 1,4,7‐triazacyclononane‐1,4,7‐triacetic acid containing sulfonamide group (18F‐Al‐NOTA‐SN) as a potential tumor‐targeting signal‐enhanced radioactive tracer in PET. SN as a tumor‐targeting group was incorporated to NOTA to make a ligand. Subsequently, this ligand reacted with Na18F and AlCl3 to produce a compound 18F‐Al‐NOTA‐SN. This compound was further characterized and its property in regard to cell cytotoxicity assay, microPET imaging, biodistribution, cell uptake assay, and tumor selectivity in vitro and in vivo, was also investigated. 18F‐Al‐NOTA‐SN possessed low cell cytotoxicity and uptake to COS‐7 and 293T healthy cells and high cell cytotoxicity and uptake to MDA‐MB‐231, HepG2, and HeLa tumor cells in vitro. Moreover, 18F‐Al‐NOTA‐SN showed good tumor‐targeting property and high PET signal enhancement of HeLa tumors, liver, and kidneys in mice, as well as the uptake ratios of tumor to blood and tumor to muscle, were 4.98 and 3.87, respectively. 18F‐Al‐NOTA‐SN can be accepted to be kidney and liver eliminated earlier and show a potential tumor‐targeting signal‐enhanced radioactive tracer in PET.

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Evaluation of a Flexible NOTA-RGD Kit Solution Using Gallium-68 from Different 68Ge/68Ga-Generators: Pharmacokinetics and Biodistribution in Nonhuman Primates and Demonstration of Solitary Pulmonary Nodule Imaging in Humans

Cited by 14 publications

References 65 publications

⁶⁸Ga-NOTA-Functionalized Ubiquicidin: Cytotoxicity, Biodistribution, Radiation Dosimetry, and First-in-Human PET/CT Imaging of Infections

⁶⁸Ga-NOTA-Functionalized Ubiquicidin: Cytotoxicity, Biodistribution, Radiation Dosimetry, and First-in-Human PET/CT Imaging of Infections

Development of a SPECT Tracer to Image c-Met Expression in a Xenograft Model of Non–Small Cell Lung Cancer

Al¹⁸F labeled sulfonamide‐conjugated positron emission tomography tracer in vivo tumor‐targeted imaging

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Evaluation of a Flexible NOTA-RGD Kit Solution Using Gallium-68 from Different 68Ge/68Ga-Generators: Pharmacokinetics and Biodistribution in Nonhuman Primates and Demonstration of Solitary Pulmonary Nodule Imaging in Humans

Cited by 14 publications

References 65 publications

68Ga-NOTA-Functionalized Ubiquicidin: Cytotoxicity, Biodistribution, Radiation Dosimetry, and First-in-Human PET/CT Imaging of Infections

68Ga-NOTA-Functionalized Ubiquicidin: Cytotoxicity, Biodistribution, Radiation Dosimetry, and First-in-Human PET/CT Imaging of Infections

Development of a SPECT Tracer to Image c-Met Expression in a Xenograft Model of Non–Small Cell Lung Cancer

Al18F labeled sulfonamide‐conjugated positron emission tomography tracer in vivo tumor‐targeted imaging

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⁶⁸Ga-NOTA-Functionalized Ubiquicidin: Cytotoxicity, Biodistribution, Radiation Dosimetry, and First-in-Human PET/CT Imaging of Infections

⁶⁸Ga-NOTA-Functionalized Ubiquicidin: Cytotoxicity, Biodistribution, Radiation Dosimetry, and First-in-Human PET/CT Imaging of Infections

Al¹⁸F labeled sulfonamide‐conjugated positron emission tomography tracer in vivo tumor‐targeted imaging