Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET

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Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET. / James, Michelle L; Shen, Bin; Nielsen, Carsten Haagen; Behera, Deepak; Buckmaster, Christine L; Mesangeau, Christophe; Zavaleta, Cristina; Vuppala, Pradeep K; Jamalapuram, Seshulatha; Avery, Bonnie A; Lyons, David M; McCurdy, Christopher R; Biswal, Sandip; Gambhir, Sanjiv S; Chin, Frederick T.

In: Journal of Nuclear Medicine, Vol. 55, No. 1, 01.2014, p. 147-53.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

James, ML, Shen, B, Nielsen, CH, Behera, D, Buckmaster, CL, Mesangeau, C, Zavaleta, C, Vuppala, PK, Jamalapuram, S, Avery, BA, Lyons, DM, McCurdy, CR, Biswal, S, Gambhir, SS & Chin, FT 2014, 'Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET', Journal of Nuclear Medicine, vol. 55, no. 1, pp. 147-53. https://doi.org/10.2967/jnumed.113.120261

APA

James, M. L., Shen, B., Nielsen, C. H., Behera, D., Buckmaster, C. L., Mesangeau, C., Zavaleta, C., Vuppala, P. K., Jamalapuram, S., Avery, B. A., Lyons, D. M., McCurdy, C. R., Biswal, S., Gambhir, S. S., & Chin, F. T. (2014). Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET. Journal of Nuclear Medicine, 55(1), 147-53. https://doi.org/10.2967/jnumed.113.120261

Vancouver

James ML, Shen B, Nielsen CH, Behera D, Buckmaster CL, Mesangeau C et al. Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET. Journal of Nuclear Medicine. 2014 Jan;55(1):147-53. https://doi.org/10.2967/jnumed.113.120261

Author

James, Michelle L ; Shen, Bin ; Nielsen, Carsten Haagen ; Behera, Deepak ; Buckmaster, Christine L ; Mesangeau, Christophe ; Zavaleta, Cristina ; Vuppala, Pradeep K ; Jamalapuram, Seshulatha ; Avery, Bonnie A ; Lyons, David M ; McCurdy, Christopher R ; Biswal, Sandip ; Gambhir, Sanjiv S ; Chin, Frederick T. / Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET. In: Journal of Nuclear Medicine. 2014 ; Vol. 55, No. 1. pp. 147-53.

Bibtex

@article{29a39248a0554e41a98e37a242947c5e,
title = "Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET",
abstract = "UNLABELLED: The noninvasive imaging of σ-1 receptors (S1Rs) could provide insight into their role in different diseases and lead to novel diagnostic/treatment strategies. The main objective of this study was to assess the S1R radiotracer (18)F-FTC-146 in rats. Preliminary squirrel monkey imaging and human serum/liver microsome studies were performed to gain information about the potential of (18)F-FTC-146 for eventual clinical translation.METHODS: The distribution and stability of (18)F-FTC-146 in rats were assessed via PET/CT, autoradiography, γ counting, and high-performance liquid chromatography (HPLC). Preliminary PET/MRI of squirrel monkey brain was conducted along with HPLC assessment of (18)F-FTC-146 stability in monkey plasma and human serum.RESULTS: Biodistribution studies showed that (18)F-FTC-146 accumulated in S1R-rich rat organs, including the lungs, pancreas, spleen, and brain. Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated (18)F-FTC-146 accumulation in all rat brain regions by approximately 85% (P < 0.001), suggesting radiotracer specificity for S1Rs. Similarly, PET/CT and autoradiography results demonstrated accumulation of (18)F-FTC-146 in rat brain regions known to contain S1Rs and that this uptake could be blocked by BD1047 pretreatment. Ex vivo analysis of (18)F-FTC-146 in the brain showed that only intact radiotracer was present at 15, 30, and 60 min, whereas rapid metabolism of residual (18)F-FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of (18)F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism, whereas (18)F-FTC-146 appeared to be stable in human serum. Finally, liver microsome studies revealed that (18)F-FTC-146 has a longer half-life in human microsomes, compared with rodents.CONCLUSION: Together, these results indicate that (18)F-FTC-146 is a promising tool for visualizing S1Rs in preclinical studies and that it has potential for mapping these sites in the human brain.",
keywords = "Animals, Azepines, Benzothiazoles, Brain, Chromatography, High Pressure Liquid, Humans, Ligands, Magnetic Resonance Imaging, Male, Mice, Microsomes, Liver, Positron-Emission Tomography, Protein Binding, Radiopharmaceuticals, Rats, Rats, Sprague-Dawley, Receptors, sigma, Saimiri, Tissue Distribution, Tomography, X-Ray Computed",
author = "James, {Michelle L} and Bin Shen and Nielsen, {Carsten Haagen} and Deepak Behera and Buckmaster, {Christine L} and Christophe Mesangeau and Cristina Zavaleta and Vuppala, {Pradeep K} and Seshulatha Jamalapuram and Avery, {Bonnie A} and Lyons, {David M} and McCurdy, {Christopher R} and Sandip Biswal and Gambhir, {Sanjiv S} and Chin, {Frederick T}",
year = "2014",
month = jan,
doi = "10.2967/jnumed.113.120261",
language = "English",
volume = "55",
pages = "147--53",
journal = "The Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine",
number = "1",

}

RIS

TY - JOUR

T1 - Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET

AU - James, Michelle L

AU - Shen, Bin

AU - Nielsen, Carsten Haagen

AU - Behera, Deepak

AU - Buckmaster, Christine L

AU - Mesangeau, Christophe

AU - Zavaleta, Cristina

AU - Vuppala, Pradeep K

AU - Jamalapuram, Seshulatha

AU - Avery, Bonnie A

AU - Lyons, David M

AU - McCurdy, Christopher R

AU - Biswal, Sandip

AU - Gambhir, Sanjiv S

AU - Chin, Frederick T

PY - 2014/1

Y1 - 2014/1

N2 - UNLABELLED: The noninvasive imaging of σ-1 receptors (S1Rs) could provide insight into their role in different diseases and lead to novel diagnostic/treatment strategies. The main objective of this study was to assess the S1R radiotracer (18)F-FTC-146 in rats. Preliminary squirrel monkey imaging and human serum/liver microsome studies were performed to gain information about the potential of (18)F-FTC-146 for eventual clinical translation.METHODS: The distribution and stability of (18)F-FTC-146 in rats were assessed via PET/CT, autoradiography, γ counting, and high-performance liquid chromatography (HPLC). Preliminary PET/MRI of squirrel monkey brain was conducted along with HPLC assessment of (18)F-FTC-146 stability in monkey plasma and human serum.RESULTS: Biodistribution studies showed that (18)F-FTC-146 accumulated in S1R-rich rat organs, including the lungs, pancreas, spleen, and brain. Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated (18)F-FTC-146 accumulation in all rat brain regions by approximately 85% (P < 0.001), suggesting radiotracer specificity for S1Rs. Similarly, PET/CT and autoradiography results demonstrated accumulation of (18)F-FTC-146 in rat brain regions known to contain S1Rs and that this uptake could be blocked by BD1047 pretreatment. Ex vivo analysis of (18)F-FTC-146 in the brain showed that only intact radiotracer was present at 15, 30, and 60 min, whereas rapid metabolism of residual (18)F-FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of (18)F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism, whereas (18)F-FTC-146 appeared to be stable in human serum. Finally, liver microsome studies revealed that (18)F-FTC-146 has a longer half-life in human microsomes, compared with rodents.CONCLUSION: Together, these results indicate that (18)F-FTC-146 is a promising tool for visualizing S1Rs in preclinical studies and that it has potential for mapping these sites in the human brain.

AB - UNLABELLED: The noninvasive imaging of σ-1 receptors (S1Rs) could provide insight into their role in different diseases and lead to novel diagnostic/treatment strategies. The main objective of this study was to assess the S1R radiotracer (18)F-FTC-146 in rats. Preliminary squirrel monkey imaging and human serum/liver microsome studies were performed to gain information about the potential of (18)F-FTC-146 for eventual clinical translation.METHODS: The distribution and stability of (18)F-FTC-146 in rats were assessed via PET/CT, autoradiography, γ counting, and high-performance liquid chromatography (HPLC). Preliminary PET/MRI of squirrel monkey brain was conducted along with HPLC assessment of (18)F-FTC-146 stability in monkey plasma and human serum.RESULTS: Biodistribution studies showed that (18)F-FTC-146 accumulated in S1R-rich rat organs, including the lungs, pancreas, spleen, and brain. Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated (18)F-FTC-146 accumulation in all rat brain regions by approximately 85% (P < 0.001), suggesting radiotracer specificity for S1Rs. Similarly, PET/CT and autoradiography results demonstrated accumulation of (18)F-FTC-146 in rat brain regions known to contain S1Rs and that this uptake could be blocked by BD1047 pretreatment. Ex vivo analysis of (18)F-FTC-146 in the brain showed that only intact radiotracer was present at 15, 30, and 60 min, whereas rapid metabolism of residual (18)F-FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of (18)F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism, whereas (18)F-FTC-146 appeared to be stable in human serum. Finally, liver microsome studies revealed that (18)F-FTC-146 has a longer half-life in human microsomes, compared with rodents.CONCLUSION: Together, these results indicate that (18)F-FTC-146 is a promising tool for visualizing S1Rs in preclinical studies and that it has potential for mapping these sites in the human brain.

KW - Animals

KW - Azepines

KW - Benzothiazoles

KW - Brain

KW - Chromatography, High Pressure Liquid

KW - Humans

KW - Ligands

KW - Magnetic Resonance Imaging

KW - Male

KW - Mice

KW - Microsomes, Liver

KW - Positron-Emission Tomography

KW - Protein Binding

KW - Radiopharmaceuticals

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, sigma

KW - Saimiri

KW - Tissue Distribution

KW - Tomography, X-Ray Computed

U2 - 10.2967/jnumed.113.120261

DO - 10.2967/jnumed.113.120261

M3 - Journal article

C2 - 24337599

VL - 55

SP - 147

EP - 153

JO - The Journal of Nuclear Medicine

JF - The Journal of Nuclear Medicine

SN - 0161-5505

IS - 1

ER -

ID: 132098743