Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer

Zhanquan He, Jeffrey L. Evelhoch, Ramzi M. Mohammad, N. Volkan Adsay, George Pettit, Vanutis K. Vaitkevicius, Fazlul H. Sarkar

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Pancreatic cancer is one of the most incurable and lethal human cancers in the United States. To facilitate development of novel therapeutic agents, we previously established an orthotopic pancreatic tumor model that closely mimics the natural biological behavior of human pancreatic cancer. In this study, magnetic resonance imaging (MRI) techniques were developed to detect tumor formation noninvasively and monitor serially tumor growth kinetics in this orthotopic model used for experimental drug testing. By using an optimized T2-weighted imaging method, we were able to distinguish human pancreas cancer from normal mouse pancreas. Orthotopic tumor formation was detected as early as day 11 after tumor cell implantation with a tumor volume as small as 12 mm3. Mice with evidence of tumor were separated into four treatment groups: control, auristatin-PE, gemcitabine, and their combination. After treatment, the mice were imaged at least three times before termination of the experiment. Comparison between MRI tumor volume measurements and tumor weights made at biopsy resulted in a correlation coefficient of 0.98. The tumor growth curves constructed from serial magnetic resonance imaging (MRI) measurements clearly showed tumor growth inhibition in treated mice compared with the control group. As expected, the group treated with the combination had the highest response rate compared with either auristatin-PE or gemcitabine alone, and the data were statistically highly significant (p < 0.004). From these results, we conclude that noninvasive MRI can be used to monitor serially therapeutic response in this orthotopic human pancreatic tumor model and can be used in the future to evaluate novel antitumor agents before human studies.

Original languageEnglish (US)
Pages (from-to)69-76
Number of pages8
JournalPancreas
Volume21
Issue number1
DOIs
StatePublished - Jul 2000

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Pancreatic Neoplasms
Magnetic Resonance Imaging
Neoplasms
gemcitabine
Tumor Burden
Therapeutics
Growth
Control Groups
Antineoplastic Agents
Pancreas
Theoretical Models
Biopsy

Keywords

  • Auristatin-PE
  • Chemotherapy
  • Orthotopic tumor growth curve
  • T1-T2

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

Cite this

Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer. / He, Zhanquan; Evelhoch, Jeffrey L.; Mohammad, Ramzi M.; Adsay, N. Volkan; Pettit, George; Vaitkevicius, Vanutis K.; Sarkar, Fazlul H.

In: Pancreas, Vol. 21, No. 1, 07.2000, p. 69-76.

Research output: Contribution to journalArticle

He, Zhanquan ; Evelhoch, Jeffrey L. ; Mohammad, Ramzi M. ; Adsay, N. Volkan ; Pettit, George ; Vaitkevicius, Vanutis K. ; Sarkar, Fazlul H. / Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer. In: Pancreas. 2000 ; Vol. 21, No. 1. pp. 69-76.
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