[18F]-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography of LAPC4-CR Castration-Resistant Prostate Cancer Xenograft Model in Soft Tissue Compartments

McCall, K; Cheng, Su–Chun; Huang, Ying; Kohl, Nancy E.; Tupper, Tanya; Abbeele, Annick D. Van den; Zukotynski, Katherine; Sweeney, Christopher J.

doi:10.1016/j.tranon.2015.03.004

Cited by 6 publications

(22 citation statements)

References 15 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Defining the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) was performed as previously described [18][19][20]. To exclude the necrotic regions of the tumor, MTV was defined as the VOI where the [ 18 F]FDG metabolism was at least 30% of the maximum activity, and mean [ 18 F]FDG uptake in MTV was measured as the mean 30% .…”

Section: Pet Imagingmentioning

confidence: 99%

“…18 F]FDG uptake after anti-PD-1 treatment in cGAMP injected mice. a Illustration of in vivo and ex vivo study timelines.…”

mentioning

confidence: 99%

“…a Illustration of in vivo and ex vivo study timelines. b Tumor growth curves after anti-PD-1 or cGAMP treatment (n =[14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Data of the non-treatment group and anti-PD-1 treated group were quoted from[11].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

et al. 2020

View full text Add to dashboard Cite

Background: Anti-programmed cell death 1 (PD-1) antibody is an immune checkpoint inhibitor, and anti-PD-1 therapy improves the anti-tumor functions of T cells and affects tumor microenvironment. We previously reported that anti-PD-1 treatment affected tumor glycolysis by using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET). That study showed that anti-PD-1 therapy in a mouse B16F10 melanoma model increased glucose metabolism in cancer cells at the point where anti-PD-1 therapy did not cause a significant inhibition of tumor growth. However, the B16F10 melanoma model is poorly immunogenic, so it is not clear how anti-PD-1 treatment affects glucose metabolism in highly immunogenic cancer models. In this study, we used a cyclic dinucleotide GMP-AMP (cGAMP)-injected B16F10 melanoma model to investigate the effect of anti-PD-1 therapy on [ 18 F]FDG uptake in a highly immune activated tumor in mice. Results: To compare the cGAMP-injected B16F10 model with the B16F10 model, experiments were performed as described in our previous manuscript. [ 18 F]FDG-PET was measured before treatment and 7 days after the start of treatment. In this study, [ 18 F]FDG uptake in tumors in the cGAMP/anti-PD-1 combination group was lower than that in the anti-PD-1 treatment group tumors on day 7, as shown by PET and ex vivo validation. Flow-cytometry was performed to assess immune cell populations and glucose metabolism. Anti-PD-1 and/or cGAMP treatment increased the infiltration level of immune cells into tumors. The cGAMP/anti-PD-1 combination group had significantly lower levels of GLUT1 high cells/hexokinase II high cells in CD45 − cancer cells compared with tumors in the anti-PD-1 treated group. These results suggested that if immune responses in tumors are higher than a certain level, glucose uptake in cancer cells is reduced depending on that level. Such a change of glucose uptake might be caused by the difference in infiltration or activation level of immune cells between the anti-PD-1 treated group and the cGAMP/anti-PD-1 combination group. Conclusions: [ 18 F]FDG uptake in cancer cells after anti-PD-1 treatment might be affected by the tumor immune microenvironment including immune cell infiltration, composition, and activation status.

show abstract

Section: Pet Imagingmentioning

confidence: 99%

“…18 F]FDG uptake after anti-PD-1 treatment in cGAMP injected mice. a Illustration of in vivo and ex vivo study timelines.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Here, we describe two novel cell lines which represent castration resistant sublines of the commonly used, androgen dependent prostate cancer cells lines LAPC4 and VCaP. It is worth noting that other groups have described similar models previously [34][35][36][37][38][39]61 . However, for many of these lines there is limited profiling data publicly available.…”

Section: Discussionmentioning

confidence: 99%

“…To help fill this need, we developed two novel CRPC cell line models which were derived from the commonly used prostate cancer cell lines, LAPC4 and VCaP 20,32,33 . Although castration resistant sublines of VCaP and LAPC4 have been used in prior studies, [34][35][36][37][38][39] . We therefore present a comprehensive characterization of LAPC4-CR and VCaP-CR models and delineate transcriptional and proteomic differences between castration resistant and parental, androgen dependent lines.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic Characterization of Two Novel Cell Line Models of Castration Resistant Prostate Cancer

Haffner

Bhamidipati

Tsai

et al. 2021

Preprint

View full text Add to dashboard Cite

BACKGROUND: Resistance to androgen deprivation therapies is a major driver of mortality in advanced prostate cancer. Therefore, there is a need to develop new pre-clinical models that allow the investigation of resistance mechanisms and the assessment of drugs for the treatment of castration resistant prostate cancer. METHODS: We generated two novel cell line models (LAPC4-CR and VCaP-CR) which were derived by passaging LAPC4 and VCaP cells in vivo and in vitro under castrate conditions. We performed detailed transcriptomic (RNA-seq) and proteomic analyses (SWATH-MS) to delineate expression differences between castration-sensitive and castration-resistant cell lines. Furthermore, we characterized the in vivo and in vitro growth characteristics of the novel cell line models. RESULTS: The two cell line derivatives LAPC4-CR and VCaP-CR showed castration resistant growth in vitro and in vivo which was only minimally inhibited by AR antagonists, enzalutamide and bicalutamide. High-dose androgen treatment resulted in significant growth arrest of VCaP-CR but not in LAPC4-CR cells. Both cell lines maintained AR expression, but exhibited distinct expression changes on the mRNA and protein level. Integrated analyses including data from LNCaP and the previously described castration resistant LNCaP-abl cells revealed an expression signature of castration resistance. CONCLUSIONS: The two novel cell line models LAPC4-CR and VCaP-CR and their comprehensive characterization on the RNA and protein level represent important resources to study the molecular mechanisms of castration resistance.

show abstract

PET/SPECT/spectral‐CT/CBCT imaging in a small‐animal radiation therapy platform: A Monte Carlo study—Part I: Quad‐modal imaging

Wang,

Li,

et al. 2024

Medical Physics

View full text Add to dashboard Cite

BackgroundIn spite of the tremendous potential of game‐changing biological image‐ and/or biologically guided radiation therapy (RT) and adaptive radiation therapy for cancer treatment, existing limited strategies for integrating molecular imaging and/or biological information with RT have impeded the translation of preclinical research findings to clinical applications. Additionally, there is an urgent need for a highly integrated small‐animal radiation therapy (SART) platform that can seamlessly combine therapeutic and diagnostic capabilities to comprehensively enhance RT for cancer treatment.PurposeWe investigated a highly integrated quad‐modal on‐board imaging configuration combining positron emission tomography (PET), single‐photon emission computed tomography (SPECT), photon‐counting spectral CT, and cone‐beam computed tomography (CBCT) in a SART platform using a Monte Carlo model as a proof‐of‐concept.MethodsThe quad‐modal on‐board imaging configuration of the SART platform was designed and evaluated by using the GATE Monte Carlo code. A partial‐ring on‐board PET imaging subsystem, utilizing advanced semiconductor thallium bromide detector technology, was designed to achieve high sensitivity and spatial resolution. On‐board SPECT, photon‐counting spectral‐CT, and CBCT imaging were performed using a single cadmium zinc telluride flat detector panel. The absolute peak sensitivity and scatter fraction of the PET subsystem were estimated by using simulated phantoms described in the NEMA NU‐4 standard. The spatial resolution of the PET image of the platform was evaluated by imaging a simulated micro‐Derenzo hot‐rod phantom. To evaluate the quantitative imaging capability of the system's spectral CT, the Bayesian eigentissue decomposition (ETD) method was utilized to quantitatively decompose the virtual noncontrast (VNC) electron densities and iodine contrast agent fractions in the Kidney1 inserts mixed with the iodine contrast agent within the simulated phantoms. The performance of the proposed quad‐model imaging in the platform was validated by imaging a simulated phantom with multiple imaging probes, including an iodine contrast agent and radioisotopes of 18F and 99mTc.ResultsThe PET subsystem demonstrated an absolute peak sensitivity of 18.5% at the scanner center, with an energy window of 175–560 KeV, and a scatter fraction of only 3.5% for the mouse phantom, with a default energy window of 480–540 KeV. The spatial resolution of PET on‐board imaging exceeded 1.2 mm. All imaging probes were identified clearly within the phantom. The PET and SPECT images agreed well with the actual spatial distributions of the tracers within the phantom. Average relative errors on electron density and iodine contrast agent fraction in the Kidney1 inserts were less than 3%. High‐quality PET images, SPECT images, spectral‐CT images (including iodine contrast agent fraction images and VNC electron density images), and CBCT images of the simulated phantom demonstrated the comprehensive multimodal imaging capability of the system.ConclusionsThe results demonstrated the feasibility of the proposed quad‐modal imaging configuration in a SART platform. The design incorporates anatomical, molecular, and functional information about tumors, thereby facilitating successful translation of preclinical studies into clinical practices.

show abstract

[18F]-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography of LAPC4-CR Castration-Resistant Prostate Cancer Xenograft Model in Soft Tissue Compartments

Cited by 6 publications

References 15 publications

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

Phenotypic Characterization of Two Novel Cell Line Models of Castration Resistant Prostate Cancer

PET/SPECT/spectral‐CT/CBCT imaging in a small‐animal radiation therapy platform: A Monte Carlo study—Part I: Quad‐modal imaging

Contact Info

Product

Resources

About