Visualization of a primary anti-tumor immune response by positron emission tomography

Shu, Chengyi J.; Guo, Shuling; Kim, Young Jin; Shelly, Stephanie M.; Nijagal, Amar; Ray, Pritha; Gambhir, Sanjiv S.; Radu, Caius G.; Witte, Owen N.

doi:10.1073/pnas.0508698102

Cited by 74 publications

(67 citation statements)

References 29 publications

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“…Animals were anesthetized with 2% isoflurane, injected i.v. with [ 18 F]FDG, and scanned by using a Focus 220 microPET scanner (Siemens, Knoxville, TN) as described (14). Images were reconstructed by using an iterative maximum a posteriori algorithm (49).…”

Section: Methodsmentioning

confidence: 99%

“…Whereas these mice mounted a strong response in the periphery against the immunizing MOG 35-55 antigen, EAE incidence was greatly reduced in this experimental group (only 3 of 47 mice developed mild EAE, with a clinical score of 1). The differential rate of glycolysis in EAE-affected mice (score of Ն1 on days [14][15][16][17] relative to that in nonimmunized mice and mice immunized with MOG /CFA only, without PTX treatment, is shown in Fig. 3B.…”

Section: Eae-affected Mice Show Higher Uptake Of [ 18 F]fdg In the Spmentioning

confidence: 99%

“…Key players include AKT, which is activated by phosphatidylinositol 3-kinase (10), and the PIM1 and PIM2 kinases, which are activated by the Janus kinase and signal transducer and activator of transcription pathway (10). In addition to that in T cells, elevated glycolysis after activation has been reported in other immune cell types such as macrophages (11) and neutrophils (12 (14). Third, examples of using [ 18 F]FDG PET to evaluate abnormal glycolysis in autoimmune disorders such as rheumatoid arthritis (15)(16)(17) and systemic lupus erythematosus (SLE) (18) can be found in the literature, albeit in much lower numbers relative to cancer studies.…”

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confidence: 99%

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Positron emission tomography with computed tomography imaging of neuroinflammation in experimental autoimmune encephalomyelitis

Radu¹,

Shu²,

Shelly³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Section: Methodsmentioning

confidence: 99%

Section: Eae-affected Mice Show Higher Uptake Of [ 18 F]fdg In the Spmentioning

confidence: 99%

mentioning

confidence: 99%

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Positron emission tomography with computed tomography imaging of neuroinflammation in experimental autoimmune encephalomyelitis

Radu¹,

Shu²,

Shelly³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Because these therapies are typically not directly acting, it is essential to monitor the time course, characteristics, and specificity of the immune response and its effect against the tumor. Both PET-and MRI-based procedures have been proposed to monitor immunotherapies [135], [136]. In terms of joint PET/MRI measurements, once again it is the qualitatively different information obtainable from the two modalities and temporal coincidence that brings real utility to the simultaneous measurement.…”

Section: Monitoring Tumor Responsementioning

confidence: 99%

The Integration of Positron Emission Tomography With Magnetic Resonance Imaging

Cherry¹,

Louie

Jacobs

2008

Proc. IEEE

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| A number of laboratories and companies are currently exploring the development of integrated imaging systems for magnetic resonance imaging (MRI) and positron emission tomography (PET). Scanners for both preclinical and human research applications are being pursued. In contrast to the widely distributed and now quite mature PET/computed tomography technology, most PET/MRI designs allow for simultaneous rather than sequential acquisition of PET and MRI data. While this offers the possibility of novel imaging strategies, it also creates considerable challenges for acquiring artifact-free images from both modalities. This paper discusses the motivation for developing combined PET/MRI technology, outlines the obstacles in realizing such an integrated instrument, and presents recent progress in the development of both the instrumentation and of novel imaging agents for combined PET/MRI studies. The performance of the first-generation PET/MRI systems is described. Finally, a range of possible biomedical applications for PET/MRI are outlined.

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“…PET and bioluminescent imaging have emerged recently as new strategies to longitudinally visualize the in vivo distribution and tumor targeting of immune cells transduced to express reporter genes. Our group and others have demonstrated the feasibility of both BLI and micro PET-based in vivo imaging approaches to monitor anti-tumor immunity [2,8,11,23,24,25,33,40,46,47,48]. In this study, we adapted BLI to allow us to test our hypothesis that T cells specific for endogenous melanoma antigens can localize into brain tumors and exert an antitumor effect.…”

Section: Introductionmentioning

confidence: 99%

Anti-tumor activity and trafficking of self, tumor-specific T cells against tumors located in the brain

Prins

Shu

Radu

et al. 2008

Cancer Immunol Immunother

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It is commonly believed that T cells have difficulty reaching tumors located in the brain due to the presumed "immune privilege" of the central nervous system (CNS). Therefore, we studied the biodistribution and antitumor activity of adoptively transferred T cells specific for an endogenous tumor-associated antigen (TAA), gp100, expressed by tumors implanted in the brain. Mice with preestablished intracranial (i.c.) tumors underwent total body irradiation (TBI) to induce transient lymphopenia, followed by the adoptive transfer of gp100 25-33 -specific CD8 + T cells (Pmel-1). Pmel-1 cells were transduced to express the bioluminescent imaging (BLI) gene luciferase. After adoptive transfer, recipient mice were vaccinated with hgp100 25-33 peptidepulsed dendritic cells (hgp100 25-33 /DC) and systemic interleukin 2 (IL-2). This treatment regimen resulted in significant reduction in tumor size and extended survival. Imaging of T cell trafficking demonstrated early accumulation of transduced T cells in lymph nodes draining the hgp100 25-33 /DC vaccination sites, the spleen and the cervical lymph nodes draining the CNS tumor. Subsequently, transduced T cells accumulated in the bone marrow and brain tumor. BLI could also detect significant differences in NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript the expansion of gp100-specific CD8 + T cells in the treatment group compared with mice that did not receive either DC vaccination or IL-2. These differences in BLI correlated with the differences seen both in survival and tumor infiltrating lymphocytes (TIL). These studies demonstrate that peripheral tolerance to endogenous TAA can be overcome to treat tumors in the brain and suggest a novel trafficking paradigm for the homing of tumor-specific T cells that target CNS tumors.

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Visualization of a primary anti-tumor immune response by positron emission tomography

Cited by 74 publications

References 29 publications

Positron emission tomography with computed tomography imaging of neuroinflammation in experimental autoimmune encephalomyelitis

Positron emission tomography with computed tomography imaging of neuroinflammation in experimental autoimmune encephalomyelitis

The Integration of Positron Emission Tomography With Magnetic Resonance Imaging

Anti-tumor activity and trafficking of self, tumor-specific T cells against tumors located in the brain

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