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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

Serial measurements of PET signal.PET signal was measured on Days 7, 10, 15, 17, 21, 24, and 28 in 5 animals.
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FIG7: Serial measurements of PET signal.PET signal was measured on Days 7, 10, 15, 17, 21, 24, and 28 in 5 animals.

Mentions: Serial PET imaging was performed at 10 time points. During PET image acquisition, the liver background signal remained constant with a mean tissue-specific uptake index of 0.04%ID/g (range 0.03-0.05). All six tumors demonstrated FDG uptake. A discrete tumor was first observed on Days 14-15 in all animals with a mean tissue-specific uptake index of 0.14%ID/g. The PET signal increased linearly with tumor growth with a maximum mean tissue-specific uptake index of 0.81%ID/g (range 0.59-0.91) on Day 28 (Figures 7-8). After Day 24, PET imaging revealed evidence of intraperitoneal tumor metastases in all animals, which was confirmed on necropsy.


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)

Serial measurements of PET signal.PET signal was measured on Days 7, 10, 15, 17, 21, 24, and 28 in 5 animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

FIG7: Serial measurements of PET signal.PET signal was measured on Days 7, 10, 15, 17, 21, 24, and 28 in 5 animals.
Mentions: Serial PET imaging was performed at 10 time points. During PET image acquisition, the liver background signal remained constant with a mean tissue-specific uptake index of 0.04%ID/g (range 0.03-0.05). All six tumors demonstrated FDG uptake. A discrete tumor was first observed on Days 14-15 in all animals with a mean tissue-specific uptake index of 0.14%ID/g. The PET signal increased linearly with tumor growth with a maximum mean tissue-specific uptake index of 0.81%ID/g (range 0.59-0.91) on Day 28 (Figures 7-8). After Day 24, PET imaging revealed evidence of intraperitoneal tumor metastases in all animals, which was confirmed on necropsy.

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