Synthesis and In Vivo Evaluation of<i>p</i>-<sup>18</sup>F-Fluorohippurate as a New Radiopharmaceutical for Assessment of Renal Function by PET

Awasthi, Vibhudutta; Pathuri, Gopal; Agashe, Hrushikesh; Gali, Hariprasad

doi:10.2967/jnumed.110.075895

Cited by 32 publications

(25 citation statements)

References 23 publications

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“…18 F]fluorohippurate was detected in the bladder within 2 min of intravenous infusion in a normal rat (2). Furthermore, we also suspect that the smaller molecular size of urea may result in faster transit than these other tracers.…”

Section: Discussionmentioning

confidence: 90%

Monitoring urea transport in rat kidney in vivo using hyperpolarized¹³C magnetic resonance imaging

Morze

Bok

Sands

et al. 2012

American Journal of Physiology-Renal Physiology

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DB. Monitoring urea transport in rat kidney in vivo using hyperpolarized 13 C magnetic resonance imaging. Am J Physiol Renal Physiol 302: F1658 -F1662, 2012. First published April 4, 2012 doi:10.1152/ajprenal.00640.2011.-Urea functions as a key osmolyte in the urinary concentrating mechanism of the inner medulla. The urea transporter UT-A1 is upregulated by antidiuretic hormone, facilitating faster equilibration of urea between the lumen and interstitium of the inner medullary collecting duct, resulting in the formation of more highly concentrated urine. New methods in dynamic nuclear polarization, providing ϳ50,000-fold enhancement of nuclear magnetic resonance signals in the liquid state, offer a novel means to monitor this process in vivo using magnetic resonance imaging. In this study, we detected significant signal differences in the rat kidney between acute diuretic and antidiuretic states, using dynamic 13 C magnetic resonance imaging following a bolus infusion of hyperpolarized [13 C]urea. More rapid medullary enhancement was observed under antidiuresis, consistent with known upregulation of UT-A1. dynamic nuclear polarization; diuresis; urinary concentrating mechanism; UT-A1 UREA PLAYS A VITAL ROLE in the urinary concentrating mechanism by functioning as a key osmolyte (19). While sodium chloride is the dominant solute in the outer medullary interstitium, urea is important in the inner medulla. In the inner medullary collecting duct (IMCD), facilitated transporters UT-A1 and UT-A3 allow specific reabsorption of urea from the luminal fluid, followed by reabsorption of water down the resulting osmotic gradient via aquaporins. A knockout mouse lacking UT-A1 and UT-A3 has been shown to have a urinary concentrating defect (4). Transport is required since urea is a highly polar molecule with subsequently low diffusivity across lipid bilayers. Activity of UT-A1 is acutely sensitive to antidiuretic hormone (or vasopressin) (11,22), facilitating faster equilibration in the concentration of urea between luminal and interstitial spaces of the inner medulla, resulting in the formation of more highly concentrated urine.Dynamic nuclear polarization (DNP) with recently developed rapid dissolution technology has enabled ϳ50,000-fold enhancement of nuclear magnetic resonance (NMR) signals in the liquid state (1). Hyperpolarization persists for a limited time according to the longitudinal T 1 relaxation time of the nucleus (on the order of 1 min for 13 C nuclei of interest). By overcoming the limitation of poor sensitivity that hampered previous studies with 13 C-labeled compounds, this development has introduced a new set of 13 C-labeled contrast agents for magnetic resonance imaging (MRI), such as [1-13 C]pyruvate, whose distribution and enzymatic conversion to lactate may be monitored in vivo (8). A current clinical trial using hyperpolarized [1-13 C]pyruvate as a MRI contrast agent in prostate cancer patients demonstrates the feasibility of this approach to investigate human disease (14). Urea, which as an end produ...

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Section: Discussionmentioning

confidence: 90%

Monitoring urea transport in rat kidney in vivo using hyperpolarized¹³C magnetic resonance imaging

Morze

Bok

Sands

et al. 2012

American Journal of Physiology-Renal Physiology

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“…To overcome this issue, we focused on drug efflux transporters at the BBB. Drug efflux transporters at the BBB limit the penetration of tracer compounds used for in vivo imaging into the brain (Syvänen et al, 2006;Wanek et al, 2012;Bakhsheshian et al, 2013;. Therefore, the inhibitors of drug efflux transporters might enhance brain uptake of […”

Section: Discussionmentioning

confidence: 99%

“…CsA has been reported to inhibit ABCB1 (P-gp) at the BBB and to enhance brain accumulation of a PET tracer at 25 mg/kg (Syvänen et al, 2006). Additionally, probenecid increased brain concentrations of some compounds at 50 -70 mg/kg (Awasthi et al, 2011;Töllner et al, 2015). In this study, CsA and probenecid were used at injected doses of 25-50 and 10 -100 mg/kg, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Drug transporters at the BBB include ATP-binding cassette (ABC) transporters, such as ABCB1 [P-glycoprotein (P-gp)], ABCG2 and ABCCs [multidrug-related resistance proteins (Mrps)], as well as solute carrier proteins, such as organic anion transporter 3 (OAT3/SLC22A8; Schinkel et al, 1996;Wijnholds et al, 2000;Sugiyama et al, 2001). The accumulation of some PET radiotracers in the brain has been improved by pretreatment with transporter inhibitors for ABCB1 (Syvänen et al, 2006;Laćan et al, 2008) or ABCG2 (Wanek et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Noninvasive Evaluation of Cellular Proliferative Activity in Brain Neurogenic Regions in Rats under Depression and Treatment by Enhanced [18F]FLT-PET Imaging

Tamura¹,

Takahashi²,

Takata³

et al. 2016

Journal of Neuroscience

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Neural stem cells in two neurogenic regions, the subventricular zone and the subgranular zone (SGZ) of the hippocampal dentate gyrus, can divide and produce new neurons throughout life. Hippocampal neurogenesis is related to emotions, including depression/anxiety, and the therapeutic effects of antidepressants, as well as learning and memory. The establishment of in vivo imaging for proliferative activity of neural stem cells in the SGZ might be used to diagnose depression and to monitor the therapeutic efficacy of antidepressants. Positron emission tomography (PET) imaging with 3Ј-deoxy-3Ј-[

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“…Recent studies [1–5] showed that joint CT/PET imaging can enable physicians to noninvasively monitor and evaluate recovery progress in patients who have undergone bone marrow transplant. With CT/PET imaging technology, anatomic details such as bone structures, kidney, and water are best captured by CT while the PET modality is capable of measuring biochemical changes inside organs.…”

Section: Introductionmentioning

confidence: 99%

An automatic 3D CT/PET segmentation framework for bone marrow proliferation assessment

Nguyen

Havlicek

Duong

et al. 2016

2016 IEEE International Conference on Image Processing (ICIP)

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Clinical assessment of bone marrow is limited by an inability to evaluate the marrow space comprehensively and dynamically and there is no current method for automatically assessing hematopoietic activity within the medullary space. Evaluating the hematopoietic space in its entirety could be applicable in blood disorders, malignancies, infections, and medication toxicity. In this paper, we introduce a CT/PET 3D automatic framework for measurement of the hematopoietic compartment proliferation within osseous sites. We first perform a full-body bone structure segmentation using 3D graph-cut on the CT volume. The vertebrae are segmented by detecting the discs between adjacent vertebrae. Finally, we register the bone marrow CT volume with its corresponding PET volume and capture the spinal bone marrow volume. The proposed framework was tested on 17 patients, achieving an average accuracy of 86.37% and a worst case accuracy of 82.3% in automatically extracting the aggregate volume of the spinal marrow cavities.

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Synthesis and In Vivo Evaluation ofp-¹⁸F-Fluorohippurate as a New Radiopharmaceutical for Assessment of Renal Function by PET

Cited by 32 publications

References 23 publications

Monitoring urea transport in rat kidney in vivo using hyperpolarized¹³C magnetic resonance imaging

Monitoring urea transport in rat kidney in vivo using hyperpolarized¹³C magnetic resonance imaging

Noninvasive Evaluation of Cellular Proliferative Activity in Brain Neurogenic Regions in Rats under Depression and Treatment by Enhanced [18F]FLT-PET Imaging

An automatic 3D CT/PET segmentation framework for bone marrow proliferation assessment

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Synthesis and In Vivo Evaluation ofp-18F-Fluorohippurate as a New Radiopharmaceutical for Assessment of Renal Function by PET

Cited by 32 publications

References 23 publications

Monitoring urea transport in rat kidney in vivo using hyperpolarized13C magnetic resonance imaging

Monitoring urea transport in rat kidney in vivo using hyperpolarized13C magnetic resonance imaging

Noninvasive Evaluation of Cellular Proliferative Activity in Brain Neurogenic Regions in Rats under Depression and Treatment by Enhanced [18F]FLT-PET Imaging

An automatic 3D CT/PET segmentation framework for bone marrow proliferation assessment

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Product

Resources

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Synthesis and In Vivo Evaluation ofp-¹⁸F-Fluorohippurate as a New Radiopharmaceutical for Assessment of Renal Function by PET

Monitoring urea transport in rat kidney in vivo using hyperpolarized¹³C magnetic resonance imaging

Monitoring urea transport in rat kidney in vivo using hyperpolarized¹³C magnetic resonance imaging