Preclinical evaluation of 18F-LMI1195 for in vivo imaging of pheochromocytoma in the MENX tumor model

Florian C. Gaertner, Tobias Wiedemann, Behrooz H. Yousefi, Misu Lee, Ines Repokis, Takahiro Higuchi, Stephan G. Nekolla, Ming Yu, Simon Robinson, Markus Schwaiger, Natalia S. Pellegata

Research output: Contribution to journalArticle

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Abstract

We evaluated 18F-LMI1195 (1-(3-bromo-4-(3-18F-fluoro- propoxy)benzyl) guanidine), a metaiodobenzylguanidine (MIBG) analog, for the detection of pheochromocytoma in a preclinical in vivo model of endogenous neuroendocrine tumors (multiple endocrine neoplasia [MENX]). Methods: Adrenal uptake kinetics of 18F-LMI1195 were evaluated in healthy Wistar rats (n 5 6) by dynamic PET imaging. Distribution of 18F-LMI1195 was evaluated in tumor-bearing MENX mut/mut rats (n 5 10) and control MENX wild-type rats (n = 4) by biodistribution studies and PET imaging. Biodistribution of 18FLMI1195 was compared with 123I-MIBG in MENX mut/mut rats (n = 6) and correlated with histological tumor volume and norepinephrine transporter (NET) expression. Uptake specificity was evaluated by in vivo inhibition of the NET by desipramine (n = 6). Intraadrenal distribution of 18F-LMI1195 was evaluated by autoradiography. Results: 18F-LMI1195 showed rapid tracer accumulation in adrenal glands 1 min after tracer injection. Adrenal glands of MENX mut/mut animals showed significantly higher standardized uptake value than MENX wild-type controls (maximum SUV, 10.3 ± 2.3 vs. 6.1 ± 0.9, P < 0.01). Adrenal uptake in MENX mut/mut rats could be inhibited by desipramine, shown by biodistribution studies (0.06 ± 0.01 vs. 0.16 ± 0.05 percentage injected dose, P < 0.01), PET imaging (maximum SUV, 3.8 ±0.8 vs. 10.3 ±2.3, P < 0.01), and autoradiography. Adrenal uptake of 18F-LMI1195 correlated with 123I-MIBG uptake (r = 0.91), histological tumor volume (r = 0.68), and NET expression (r = 0.50). 18F-LMI1195 showed an overall favorable distribution for tumor imaging. Conclusion: 18F-LMI1195 shows high and specific accumulation in pheochromocytomas. Its favorable biodistribution makes it a promising PET tracer for tumor imaging. Further studies are warranted to evaluate its clinical value in oncologic indications. COPYRIGHT

Original languageEnglish
Pages (from-to)2111-2117
Number of pages7
JournalJournal of Nuclear Medicine
Volume54
Issue number12
DOIs
Publication statusPublished - Dec 1 2013
Externally publishedYes

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Pheochromocytoma
Norepinephrine Plasma Membrane Transport Proteins
Neoplasms
Desipramine
Adrenal Glands
Tumor Burden
Autoradiography
Multiple Endocrine Neoplasia
Neuroendocrine Tumors
N-(3-bromo-4-(3-(18F)fluoro-propoxy)benzyl)guanidine
Guanidine
Wistar Rats
Injections

Keywords

  • MENX
  • MIBG
  • Oncology
  • Pheochromocytoma

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Gaertner, F. C., Wiedemann, T., Yousefi, B. H., Lee, M., Repokis, I., Higuchi, T., ... Pellegata, N. S. (2013). Preclinical evaluation of 18F-LMI1195 for in vivo imaging of pheochromocytoma in the MENX tumor model. Journal of Nuclear Medicine, 54(12), 2111-2117. https://doi.org/10.2967/jnumed.113.119966

Preclinical evaluation of 18F-LMI1195 for in vivo imaging of pheochromocytoma in the MENX tumor model. / Gaertner, Florian C.; Wiedemann, Tobias; Yousefi, Behrooz H.; Lee, Misu; Repokis, Ines; Higuchi, Takahiro; Nekolla, Stephan G.; Yu, Ming; Robinson, Simon; Schwaiger, Markus; Pellegata, Natalia S.

In: Journal of Nuclear Medicine, Vol. 54, No. 12, 01.12.2013, p. 2111-2117.

Research output: Contribution to journalArticle

Gaertner, FC, Wiedemann, T, Yousefi, BH, Lee, M, Repokis, I, Higuchi, T, Nekolla, SG, Yu, M, Robinson, S, Schwaiger, M & Pellegata, NS 2013, 'Preclinical evaluation of 18F-LMI1195 for in vivo imaging of pheochromocytoma in the MENX tumor model', Journal of Nuclear Medicine, vol. 54, no. 12, pp. 2111-2117. https://doi.org/10.2967/jnumed.113.119966
Gaertner, Florian C. ; Wiedemann, Tobias ; Yousefi, Behrooz H. ; Lee, Misu ; Repokis, Ines ; Higuchi, Takahiro ; Nekolla, Stephan G. ; Yu, Ming ; Robinson, Simon ; Schwaiger, Markus ; Pellegata, Natalia S. / Preclinical evaluation of 18F-LMI1195 for in vivo imaging of pheochromocytoma in the MENX tumor model. In: Journal of Nuclear Medicine. 2013 ; Vol. 54, No. 12. pp. 2111-2117.
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abstract = "We evaluated 18F-LMI1195 (1-(3-bromo-4-(3-18F-fluoro- propoxy)benzyl) guanidine), a metaiodobenzylguanidine (MIBG) analog, for the detection of pheochromocytoma in a preclinical in vivo model of endogenous neuroendocrine tumors (multiple endocrine neoplasia [MENX]). Methods: Adrenal uptake kinetics of 18F-LMI1195 were evaluated in healthy Wistar rats (n 5 6) by dynamic PET imaging. Distribution of 18F-LMI1195 was evaluated in tumor-bearing MENX mut/mut rats (n 5 10) and control MENX wild-type rats (n = 4) by biodistribution studies and PET imaging. Biodistribution of 18FLMI1195 was compared with 123I-MIBG in MENX mut/mut rats (n = 6) and correlated with histological tumor volume and norepinephrine transporter (NET) expression. Uptake specificity was evaluated by in vivo inhibition of the NET by desipramine (n = 6). Intraadrenal distribution of 18F-LMI1195 was evaluated by autoradiography. Results: 18F-LMI1195 showed rapid tracer accumulation in adrenal glands 1 min after tracer injection. Adrenal glands of MENX mut/mut animals showed significantly higher standardized uptake value than MENX wild-type controls (maximum SUV, 10.3 ± 2.3 vs. 6.1 ± 0.9, P < 0.01). Adrenal uptake in MENX mut/mut rats could be inhibited by desipramine, shown by biodistribution studies (0.06 ± 0.01 vs. 0.16 ± 0.05 percentage injected dose, P < 0.01), PET imaging (maximum SUV, 3.8 ±0.8 vs. 10.3 ±2.3, P < 0.01), and autoradiography. Adrenal uptake of 18F-LMI1195 correlated with 123I-MIBG uptake (r = 0.91), histological tumor volume (r = 0.68), and NET expression (r = 0.50). 18F-LMI1195 showed an overall favorable distribution for tumor imaging. Conclusion: 18F-LMI1195 shows high and specific accumulation in pheochromocytomas. Its favorable biodistribution makes it a promising PET tracer for tumor imaging. Further studies are warranted to evaluate its clinical value in oncologic indications. COPYRIGHT",
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AU - Wiedemann, Tobias

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AU - Lee, Misu

AU - Repokis, Ines

AU - Higuchi, Takahiro

AU - Nekolla, Stephan G.

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