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Development of a High-Throughput Molecular Imaging-Based Orthotopic Hepatocellular Carcinoma Model.

Hwang GL, van den Bosch MA, Kim YI, Katzenberg R, Willmann JK, Paulmurugan R, Gambhir SS, Hofmann L - Cureus (2015)

Bottom Line: In six animals, serial PET, BLI, and ultrasound imaging were performed at 10-time points in 28 days.The first metastases were detected by PET after Day 24.        We have successfully developed and validated a novel orthotopic HCC small animal model that permits longitudinal assessment of change in tumor size using molecular imaging techniques.This model permits high-throughput in vivo evaluation of image-guided therapies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Radiology, Stanford University School of Medicine.

ABSTRACT
We have developed a novel orthotopic rat hepatocellular (HCC) model and have assessed the ability to use bioluminescence imaging (BLI), positron emission tomography (PET), and ultrasound for early tumor detection and monitoring of disease progression.  Briefly, rat HCC cells were stably transfected with click beetle red as a reporter gene for BLI. Tumor cells were injected under direct visualization into the left or middle lobe of the liver in 37 rats. In six animals, serial PET, BLI, and ultrasound imaging were performed at 10-time points in 28 days. The remainder of the animals underwent PET imaging at 14 days. Tumor implantation was successful in 34 of 37 animals (91.9%). In the six animals that underwent serial imaging, tumor formation was first detected with BLI on Day 4 with continued increase through Day 21, and hypermetabolic activity on PET was first noted on Days 14-15 with continued increase through Day 28. PET activity was seen on Day 14 in the 28 other animals that demonstrated tumor development. Anatomic tumor formation was detected with ultrasound at Days 10-12 with continued growth through Day 28. The first metastases were detected by PET after Day 24.        We have successfully developed and validated a novel orthotopic HCC small animal model that permits longitudinal assessment of change in tumor size using molecular imaging techniques. BLI is the most sensitive imaging method for detection of early tumor formation and growth. This model permits high-throughput in vivo evaluation of image-guided therapies.

No MeSH data available.


Related in: MedlinePlus

Representative gross and histopathologic specimen of Morris HCC. 5x view reveals a sharp demarcation between the implanted tumor (upper field) and the normal liver (lower field), with evidence of hypervascularity within the tumor. 20x view demonstrates that compared with normal liver (a), the HCC (b) demonstrates poorly differentiated cells, with markedly increased mitotic activity and hyperchromatism. (c) Grossly, the tumor (arrow) is pale and well-circumscribed and extends to the liver capsule.
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FIG2: Representative gross and histopathologic specimen of Morris HCC. 5x view reveals a sharp demarcation between the implanted tumor (upper field) and the normal liver (lower field), with evidence of hypervascularity within the tumor. 20x view demonstrates that compared with normal liver (a), the HCC (b) demonstrates poorly differentiated cells, with markedly increased mitotic activity and hyperchromatism. (c) Grossly, the tumor (arrow) is pale and well-circumscribed and extends to the liver capsule.

Mentions: After final imaging on Day 28, the animals were euthanized by carbon dioxide inhalation. A midline laparotomy was performed and the liver and peritoneal cavity were inspected prior to explantation of the liver. Gross pathology and hematoxylin-eosin staining from a representative liver specimen are shown in Figure 2.


Development of a High-Throughput Molecular Imaging-Based Orthotopic Hepatocellular Carcinoma Model.

Hwang GL, van den Bosch MA, Kim YI, Katzenberg R, Willmann JK, Paulmurugan R, Gambhir SS, Hofmann L - Cureus (2015)

Representative gross and histopathologic specimen of Morris HCC. 5x view reveals a sharp demarcation between the implanted tumor (upper field) and the normal liver (lower field), with evidence of hypervascularity within the tumor. 20x view demonstrates that compared with normal liver (a), the HCC (b) demonstrates poorly differentiated cells, with markedly increased mitotic activity and hyperchromatism. (c) Grossly, the tumor (arrow) is pale and well-circumscribed and extends to the liver capsule.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494575&req=5

FIG2: Representative gross and histopathologic specimen of Morris HCC. 5x view reveals a sharp demarcation between the implanted tumor (upper field) and the normal liver (lower field), with evidence of hypervascularity within the tumor. 20x view demonstrates that compared with normal liver (a), the HCC (b) demonstrates poorly differentiated cells, with markedly increased mitotic activity and hyperchromatism. (c) Grossly, the tumor (arrow) is pale and well-circumscribed and extends to the liver capsule.
Mentions: After final imaging on Day 28, the animals were euthanized by carbon dioxide inhalation. A midline laparotomy was performed and the liver and peritoneal cavity were inspected prior to explantation of the liver. Gross pathology and hematoxylin-eosin staining from a representative liver specimen are shown in Figure 2.

Bottom Line: In six animals, serial PET, BLI, and ultrasound imaging were performed at 10-time points in 28 days.The first metastases were detected by PET after Day 24.        We have successfully developed and validated a novel orthotopic HCC small animal model that permits longitudinal assessment of change in tumor size using molecular imaging techniques.This model permits high-throughput in vivo evaluation of image-guided therapies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Radiology, Stanford University School of Medicine.

ABSTRACT
We have developed a novel orthotopic rat hepatocellular (HCC) model and have assessed the ability to use bioluminescence imaging (BLI), positron emission tomography (PET), and ultrasound for early tumor detection and monitoring of disease progression.  Briefly, rat HCC cells were stably transfected with click beetle red as a reporter gene for BLI. Tumor cells were injected under direct visualization into the left or middle lobe of the liver in 37 rats. In six animals, serial PET, BLI, and ultrasound imaging were performed at 10-time points in 28 days. The remainder of the animals underwent PET imaging at 14 days. Tumor implantation was successful in 34 of 37 animals (91.9%). In the six animals that underwent serial imaging, tumor formation was first detected with BLI on Day 4 with continued increase through Day 21, and hypermetabolic activity on PET was first noted on Days 14-15 with continued increase through Day 28. PET activity was seen on Day 14 in the 28 other animals that demonstrated tumor development. Anatomic tumor formation was detected with ultrasound at Days 10-12 with continued growth through Day 28. The first metastases were detected by PET after Day 24.        We have successfully developed and validated a novel orthotopic HCC small animal model that permits longitudinal assessment of change in tumor size using molecular imaging techniques. BLI is the most sensitive imaging method for detection of early tumor formation and growth. This model permits high-throughput in vivo evaluation of image-guided therapies.

No MeSH data available.


Related in: MedlinePlus