Study of the tissue distribution of TLQP-21 in mice using [18F]JMV5763, a radiolabeled Analog prepared via [18F]aluminum fluoride chelation chemistry

EA Turolla, Silvia Valtorta, E Bresciani, JA Fehrentz, L Giuliano, S Stucchi, Sara Belloli, P Rainone, F Sudati, Laura Rizzi, L Molteni, P Verdiè, J Martinez, Antonio Torsello, Rosa Maria Moresco, Sergio Todde

Research output: Contribution to journalArticle

Abstract

TLQP-21 is a neuropeptide that is involved in the control of several physiological functions, including energy homeostasis. Since TLQP-21 could oppose the early phase of diet-induced obesity, it has raised a huge interest, but very little is known about its mechanisms of action on peripheral tissues. Our aim was to investigate TLQP-21 distribution in brain and peripheral tissues after systemic administration using positron emission tomography. We report here the radiolabeling of NODA-methyl phenylacetic acid (MPAA) functionalized JMV5763, a short analog of TLQP-21, with [18F]aluminum fluoride. Labeling of JMV5763 was initially performed manually, on a small scale, and then optimized and implemented on a fully automated radiosynthesis system. In the first experiment, mice were injected in the tail vein with [18F]JMV5763, and central and peripheral tissues were collected 13, 30, and 60 min after injection. Significant uptake of [18F]JMV5763 was found in stomach, intestine, kidney, liver, and adrenal gland. In the CNS, very low uptake values were measured in all tested areas, suggesting that the tracer does not efficiently cross the blood-brain barrier. Pretreatment with non-radioactive JMV5763 caused a significant reduction of tracer uptake only in stomach and intestine. In the second experiment, PET analysis was performed in vivo 10-120 min after i.v. [18F]JMV5763 administration. Results were consistent with those of the ex vivo determinations. PET images showed a progressive increase of [18F]JMV5763 uptake in intestine and stomach reaching a peak at 30 min, and decreasing at 120 min. Our results demonstrate that 18F-labeling of TLQP-21 analogs is a suitable method to study its distribution in the body. © 2018 Turolla, Valtorta, Bresciani, Fehrentz, Giuliano, Stucchi, Belloli, Rainone, Sudati, Rizzi, Molteni, Verdiè, Martinez, Torsello, Moresco and Todde.
Original languageEnglish
Article number1274
JournalFrontiers in Pharmacology
Volume9
DOIs
Publication statusPublished - 2018
Externally publishedYes

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Tissue Distribution
Intestines
Stomach
Adrenal Glands
Neuropeptides
Blood-Brain Barrier
Positron-Emission Tomography
Tail
Veins
Homeostasis
Obesity
Diet
Kidney
Injections
Liver
Brain
aluminum fluoride

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Study of the tissue distribution of TLQP-21 in mice using [18F]JMV5763, a radiolabeled Analog prepared via [18F]aluminum fluoride chelation chemistry. / Turolla, EA; Valtorta, Silvia; Bresciani, E; Fehrentz, JA; Giuliano, L; Stucchi, S; Belloli, Sara; Rainone, P; Sudati, F; Rizzi, Laura; Molteni, L; Verdiè, P; Martinez, J; Torsello, Antonio; Moresco, Rosa Maria; Todde, Sergio.

In: Frontiers in Pharmacology, Vol. 9, 1274, 2018.

Research output: Contribution to journalArticle

Turolla, EA, Valtorta, S, Bresciani, E, Fehrentz, JA, Giuliano, L, Stucchi, S, Belloli, S, Rainone, P, Sudati, F, Rizzi, L, Molteni, L, Verdiè, P, Martinez, J, Torsello, A, Moresco, RM & Todde, S 2018, 'Study of the tissue distribution of TLQP-21 in mice using [18F]JMV5763, a radiolabeled Analog prepared via [18F]aluminum fluoride chelation chemistry', Frontiers in Pharmacology, vol. 9, 1274. https://doi.org/10.3389/fphar.2018.01274
Turolla, EA ; Valtorta, Silvia ; Bresciani, E ; Fehrentz, JA ; Giuliano, L ; Stucchi, S ; Belloli, Sara ; Rainone, P ; Sudati, F ; Rizzi, Laura ; Molteni, L ; Verdiè, P ; Martinez, J ; Torsello, Antonio ; Moresco, Rosa Maria ; Todde, Sergio. / Study of the tissue distribution of TLQP-21 in mice using [18F]JMV5763, a radiolabeled Analog prepared via [18F]aluminum fluoride chelation chemistry. In: Frontiers in Pharmacology. 2018 ; Vol. 9.
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abstract = "TLQP-21 is a neuropeptide that is involved in the control of several physiological functions, including energy homeostasis. Since TLQP-21 could oppose the early phase of diet-induced obesity, it has raised a huge interest, but very little is known about its mechanisms of action on peripheral tissues. Our aim was to investigate TLQP-21 distribution in brain and peripheral tissues after systemic administration using positron emission tomography. We report here the radiolabeling of NODA-methyl phenylacetic acid (MPAA) functionalized JMV5763, a short analog of TLQP-21, with [18F]aluminum fluoride. Labeling of JMV5763 was initially performed manually, on a small scale, and then optimized and implemented on a fully automated radiosynthesis system. In the first experiment, mice were injected in the tail vein with [18F]JMV5763, and central and peripheral tissues were collected 13, 30, and 60 min after injection. Significant uptake of [18F]JMV5763 was found in stomach, intestine, kidney, liver, and adrenal gland. In the CNS, very low uptake values were measured in all tested areas, suggesting that the tracer does not efficiently cross the blood-brain barrier. Pretreatment with non-radioactive JMV5763 caused a significant reduction of tracer uptake only in stomach and intestine. In the second experiment, PET analysis was performed in vivo 10-120 min after i.v. [18F]JMV5763 administration. Results were consistent with those of the ex vivo determinations. PET images showed a progressive increase of [18F]JMV5763 uptake in intestine and stomach reaching a peak at 30 min, and decreasing at 120 min. Our results demonstrate that 18F-labeling of TLQP-21 analogs is a suitable method to study its distribution in the body. {\circledC} 2018 Turolla, Valtorta, Bresciani, Fehrentz, Giuliano, Stucchi, Belloli, Rainone, Sudati, Rizzi, Molteni, Verdi{\`e}, Martinez, Torsello, Moresco and Todde.",
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AU - Turolla, EA

AU - Valtorta, Silvia

AU - Bresciani, E

AU - Fehrentz, JA

AU - Giuliano, L

AU - Stucchi, S

AU - Belloli, Sara

AU - Rainone, P

AU - Sudati, F

AU - Rizzi, Laura

AU - Molteni, L

AU - Verdiè, P

AU - Martinez, J

AU - Torsello, Antonio

AU - Moresco, Rosa Maria

AU - Todde, Sergio

PY - 2018

Y1 - 2018

N2 - TLQP-21 is a neuropeptide that is involved in the control of several physiological functions, including energy homeostasis. Since TLQP-21 could oppose the early phase of diet-induced obesity, it has raised a huge interest, but very little is known about its mechanisms of action on peripheral tissues. Our aim was to investigate TLQP-21 distribution in brain and peripheral tissues after systemic administration using positron emission tomography. We report here the radiolabeling of NODA-methyl phenylacetic acid (MPAA) functionalized JMV5763, a short analog of TLQP-21, with [18F]aluminum fluoride. Labeling of JMV5763 was initially performed manually, on a small scale, and then optimized and implemented on a fully automated radiosynthesis system. In the first experiment, mice were injected in the tail vein with [18F]JMV5763, and central and peripheral tissues were collected 13, 30, and 60 min after injection. Significant uptake of [18F]JMV5763 was found in stomach, intestine, kidney, liver, and adrenal gland. In the CNS, very low uptake values were measured in all tested areas, suggesting that the tracer does not efficiently cross the blood-brain barrier. Pretreatment with non-radioactive JMV5763 caused a significant reduction of tracer uptake only in stomach and intestine. In the second experiment, PET analysis was performed in vivo 10-120 min after i.v. [18F]JMV5763 administration. Results were consistent with those of the ex vivo determinations. PET images showed a progressive increase of [18F]JMV5763 uptake in intestine and stomach reaching a peak at 30 min, and decreasing at 120 min. Our results demonstrate that 18F-labeling of TLQP-21 analogs is a suitable method to study its distribution in the body. © 2018 Turolla, Valtorta, Bresciani, Fehrentz, Giuliano, Stucchi, Belloli, Rainone, Sudati, Rizzi, Molteni, Verdiè, Martinez, Torsello, Moresco and Todde.

AB - TLQP-21 is a neuropeptide that is involved in the control of several physiological functions, including energy homeostasis. Since TLQP-21 could oppose the early phase of diet-induced obesity, it has raised a huge interest, but very little is known about its mechanisms of action on peripheral tissues. Our aim was to investigate TLQP-21 distribution in brain and peripheral tissues after systemic administration using positron emission tomography. We report here the radiolabeling of NODA-methyl phenylacetic acid (MPAA) functionalized JMV5763, a short analog of TLQP-21, with [18F]aluminum fluoride. Labeling of JMV5763 was initially performed manually, on a small scale, and then optimized and implemented on a fully automated radiosynthesis system. In the first experiment, mice were injected in the tail vein with [18F]JMV5763, and central and peripheral tissues were collected 13, 30, and 60 min after injection. Significant uptake of [18F]JMV5763 was found in stomach, intestine, kidney, liver, and adrenal gland. In the CNS, very low uptake values were measured in all tested areas, suggesting that the tracer does not efficiently cross the blood-brain barrier. Pretreatment with non-radioactive JMV5763 caused a significant reduction of tracer uptake only in stomach and intestine. In the second experiment, PET analysis was performed in vivo 10-120 min after i.v. [18F]JMV5763 administration. Results were consistent with those of the ex vivo determinations. PET images showed a progressive increase of [18F]JMV5763 uptake in intestine and stomach reaching a peak at 30 min, and decreasing at 120 min. Our results demonstrate that 18F-labeling of TLQP-21 analogs is a suitable method to study its distribution in the body. © 2018 Turolla, Valtorta, Bresciani, Fehrentz, Giuliano, Stucchi, Belloli, Rainone, Sudati, Rizzi, Molteni, Verdiè, Martinez, Torsello, Moresco and Todde.

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JO - Frontiers in Pharmacology

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