Advances in preclinical therapeutics development using small animal imaging and molecular analyses: The gastrointestinal stromal tumors model

M. A. Pantaleo, L. Landuzzi, G. Nicoletti, C. Nanni, S. Boschi, G. Piazzi, D. Santini, M. Di Battista, P. Castellucci, F. Lodi, S. Fanti, P. L. Lollini, G. Biasco

Research output: Contribution to journalArticle

Abstract

The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.

Original languageEnglish
Pages (from-to)199-205
Number of pages7
JournalClinical and Experimental Medicine
Volume9
Issue number3
DOIs
Publication statusPublished - Sep 2009

Fingerprint

Gastrointestinal Stromal Tumors
Molecular Imaging
Tumors
Animals
Imaging techniques
Neoplasms
Therapeutics
Animal Models
Metabolism
Drug Combinations
Enzyme inhibition
Molecular imaging
Tumor Cell Line
Research
Heterografts
Nude Mice
Cell proliferation
Exons
Cell growth
Cell Proliferation

Keywords

  • 18-Fluoro-deoxiglucose (FDG)
  • 18-Fluoro-deoxythymidine (FLT)
  • Gastrointestinal stromal tumors (GISTs)
  • Small animal PET
  • Tyrosine kinase (TK) inhibitors

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Advances in preclinical therapeutics development using small animal imaging and molecular analyses : The gastrointestinal stromal tumors model. / Pantaleo, M. A.; Landuzzi, L.; Nicoletti, G.; Nanni, C.; Boschi, S.; Piazzi, G.; Santini, D.; Di Battista, M.; Castellucci, P.; Lodi, F.; Fanti, S.; Lollini, P. L.; Biasco, G.

In: Clinical and Experimental Medicine, Vol. 9, No. 3, 09.2009, p. 199-205.

Research output: Contribution to journalArticle

Pantaleo, MA, Landuzzi, L, Nicoletti, G, Nanni, C, Boschi, S, Piazzi, G, Santini, D, Di Battista, M, Castellucci, P, Lodi, F, Fanti, S, Lollini, PL & Biasco, G 2009, 'Advances in preclinical therapeutics development using small animal imaging and molecular analyses: The gastrointestinal stromal tumors model', Clinical and Experimental Medicine, vol. 9, no. 3, pp. 199-205. https://doi.org/10.1007/s10238-009-0033-5
Pantaleo, M. A. ; Landuzzi, L. ; Nicoletti, G. ; Nanni, C. ; Boschi, S. ; Piazzi, G. ; Santini, D. ; Di Battista, M. ; Castellucci, P. ; Lodi, F. ; Fanti, S. ; Lollini, P. L. ; Biasco, G. / Advances in preclinical therapeutics development using small animal imaging and molecular analyses : The gastrointestinal stromal tumors model. In: Clinical and Experimental Medicine. 2009 ; Vol. 9, No. 3. pp. 199-205.
@article{4a7a21adb83649b5b52a7a76dd800edc,
title = "Advances in preclinical therapeutics development using small animal imaging and molecular analyses: The gastrointestinal stromal tumors model",
abstract = "The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.",
keywords = "18-Fluoro-deoxiglucose (FDG), 18-Fluoro-deoxythymidine (FLT), Gastrointestinal stromal tumors (GISTs), Small animal PET, Tyrosine kinase (TK) inhibitors",
author = "Pantaleo, {M. A.} and L. Landuzzi and G. Nicoletti and C. Nanni and S. Boschi and G. Piazzi and D. Santini and {Di Battista}, M. and P. Castellucci and F. Lodi and S. Fanti and Lollini, {P. L.} and G. Biasco",
year = "2009",
month = "9",
doi = "10.1007/s10238-009-0033-5",
language = "English",
volume = "9",
pages = "199--205",
journal = "Zeitschrift für Die Gesamte Experimentelle Medizin",
issn = "1591-8890",
publisher = "Springer-Verlag Italia",
number = "3",

}

TY - JOUR

T1 - Advances in preclinical therapeutics development using small animal imaging and molecular analyses

T2 - The gastrointestinal stromal tumors model

AU - Pantaleo, M. A.

AU - Landuzzi, L.

AU - Nicoletti, G.

AU - Nanni, C.

AU - Boschi, S.

AU - Piazzi, G.

AU - Santini, D.

AU - Di Battista, M.

AU - Castellucci, P.

AU - Lodi, F.

AU - Fanti, S.

AU - Lollini, P. L.

AU - Biasco, G.

PY - 2009/9

Y1 - 2009/9

N2 - The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.

AB - The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.

KW - 18-Fluoro-deoxiglucose (FDG)

KW - 18-Fluoro-deoxythymidine (FLT)

KW - Gastrointestinal stromal tumors (GISTs)

KW - Small animal PET

KW - Tyrosine kinase (TK) inhibitors

UR - http://www.scopus.com/inward/record.url?scp=70349787591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349787591&partnerID=8YFLogxK

U2 - 10.1007/s10238-009-0033-5

DO - 10.1007/s10238-009-0033-5

M3 - Article

C2 - 19225718

AN - SCOPUS:70349787591

VL - 9

SP - 199

EP - 205

JO - Zeitschrift für Die Gesamte Experimentelle Medizin

JF - Zeitschrift für Die Gesamte Experimentelle Medizin

SN - 1591-8890

IS - 3

ER -