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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

Implantation of McA-RH7777-CBRluc cells into the Buffalo rat.Through a subxiphoid vertical incision, 1.0x10^6 cells in 100µl phosphate-buffered saline was injected under direct visualization into the left lobe.
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FIG1: Implantation of McA-RH7777-CBRluc cells into the Buffalo rat.Through a subxiphoid vertical incision, 1.0x10^6 cells in 100µl phosphate-buffered saline was injected under direct visualization into the left lobe.

Mentions: Our study protocol (Protocol #26869) was approved and monitored by the Stanford Institutional Administrative Panel on Laboratory Animal Care and performed in concordance with the ethical treatment of animals. Tumor implantation was performed in six adult male Buffalo rats (300-450 gm.) (Charles River Laboratories, Wilmington, MA). The procedure was done under anesthesia with 2% isoflurane in oxygen at 2 L/min on a heated platform. A longitudinal subxiphoid incision of approximately 2 cm was made to expose the liver. Log phase, reporter-tagged HCC cells (1.0x10^6 McA-RH7777-CBRluc in 100µL phosphate-buffered saline), used within 25 passages from the time of transduction, were injected under direct visualization through a 30-gauge needle into the left lateral lobe of the liver (Figure 1). The injection site was compressed for one minute with a cotton swab to prevent cell leakage out of the liver and/or bleeding into the abdominal cavity. The incision was closed with 4-0 chromic gut suture (Ethicon, Inc., Somerville, NJ). The animals were fed ad libitum and monitored daily.


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)

Implantation of McA-RH7777-CBRluc cells into the Buffalo rat.Through a subxiphoid vertical incision, 1.0x10^6 cells in 100µl phosphate-buffered saline was injected under direct visualization into the left lobe.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

FIG1: Implantation of McA-RH7777-CBRluc cells into the Buffalo rat.Through a subxiphoid vertical incision, 1.0x10^6 cells in 100µl phosphate-buffered saline was injected under direct visualization into the left lobe.
Mentions: Our study protocol (Protocol #26869) was approved and monitored by the Stanford Institutional Administrative Panel on Laboratory Animal Care and performed in concordance with the ethical treatment of animals. Tumor implantation was performed in six adult male Buffalo rats (300-450 gm.) (Charles River Laboratories, Wilmington, MA). The procedure was done under anesthesia with 2% isoflurane in oxygen at 2 L/min on a heated platform. A longitudinal subxiphoid incision of approximately 2 cm was made to expose the liver. Log phase, reporter-tagged HCC cells (1.0x10^6 McA-RH7777-CBRluc in 100µL phosphate-buffered saline), used within 25 passages from the time of transduction, were injected under direct visualization through a 30-gauge needle into the left lateral lobe of the liver (Figure 1). The injection site was compressed for one minute with a cotton swab to prevent cell leakage out of the liver and/or bleeding into the abdominal cavity. The incision was closed with 4-0 chromic gut suture (Ethicon, Inc., Somerville, NJ). The animals were fed ad libitum and monitored daily.

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