Evaluation of 18-F-fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) as a staging and monitoring tool for dogs with stage-2 splenic hemangiosarcoma – A pilot study

<div><p>Positron Emission Tomography-Computed Tomography (PET-CT) is routinely used for staging and monitoring of human cancer patients and is becoming increasingly available in veterinary medicine. In this study, 18-fluorodeoxyglucose (¹⁸FDG)-PET-CT was used in dogs with naturally occurring splenic hemangiosarcoma (HSA) to assess its utility as a staging and monitoring modality as compared to standard radiography and ultrasonography. Nine dogs with stage-2 HSA underwent ¹⁸FDG-PET-CT following splenectomy and prior to commencement of chemotherapy. Routine staging (thoracic radiography and abdominal ultrasonography) was performed prior to ¹⁸FDG-PET-CT in all dogs. When abnormalities not identified on routine tests were noted on ¹⁸FDG-PET-CT, owners were given the option to repeat a PET-CT following treatment with eBAT. A PET-CT scan was repeated on Day 21 in three dogs. Abnormalities not observed on conventional staging tools, and most consistent with malignant disease based on location, appearance, and outcome, were detected in two dogs and included a right atrial mass and a hepatic nodule, respectively. These lesions were larger and had higher metabolic activity on the second scans. ¹⁸FDG-PET-CT has potential to provide important prognostic information and influence treatment recommendations for dogs with stage-2 HSA. Additional studies will be needed to precisely define the value of this imaging tool for staging and therapy monitoring in dogs with this and other cancers.</p></div

PET-CT scan #1 from dog 2.

<p>The images from left to right are transverse (A, B, and C), sagittal (D), and dorsal plane (E), all acquired 1 hour following ¹⁸FGD injection. A and B represent the CT and PET transverse images, respectively, whereas C is the fused PET-CT transverse image. D represents the whole body ¹⁸FDG PET-CT scan, and E is the dorsal reconstruction whole body image. Fused and dorsal reconstruction images show increased metabolic activity at the right auricular appendage compared to background tissue. The focal area of uptake at the right auricular appendage is highlighted by the arrow.</p

PET-CT scan #2 from dog 6.

<p>The images from left to right are transverse (A, B, and C), sagittal (D), and dorsal plane (E), all acquired 1 hour following ¹⁸FGD injection. A and B represent the CT and PET transverse images, respectively, whereas C is the fused PET-CT transverse image. D represents the whole body ¹⁸FDG PET-CT scan, and E is the dorsal reconstruction whole body image. The focal area of uptake in the liver in proximity of the apex of the gall bladder is larger and exhibits further increase in metabolic activity compared to PET-CT #1.</p

PET-CT scan #2 from dog 2.

<p>The images from left to right are transverse (A, B, and C), sagittal (D), and dorsal plane (E), all acquired 1 hour following ¹⁸FGD injection. A and B represent the CT and PET transverse images, respectively, whereas C is the fused PET-CT transverse image. D represents the whole body ¹⁸FDG PET-CT scan, and E is the dorsal reconstruction whole body image. Fused and dorsal reconstruction images show further increase in metabolic activity at the right auricular appendage compared to background tissue and growth of the right auricular mass compared to images obtained from PET-CT scan #1. The focal area of uptake at the right auricular appendage is highlighted by the arrow.</p

Subject demographics.

<p>Subject demographics.</p

Trends in quality of life in dogs treated with KPT-335.

<p>An overall score was created based on answers to questions on the quality of life questionnaire. The scores from each question were summed resulting in an overall quality of life score which could range from 23 to 115. These are represented graphically in the figure above where scores for each patient are graphed over time (each line represents a patient). Trends in quality of life during the study were examined using linear mixed models. The overall quality of life did not change significantly in dogs treated in either the (A) dose escalation study (p = 0.64) or (B) dose expansion study (p = 0.47).</p

Hepatic and hematologic toxicities.

<p>Hepatic and hematologic toxicities.</p

Biologic activity of SINE compounds against canine tumor cell lines.

<p>Canine tumor cell lines C2 (mast cell), OSA16 (osteosarcoma) and 323610-3 were cultured in 96 well plates in triplicate with serial dilutions of KPT-214 for 92 hours after which the plates were collected, media removed, and the plates were frozen at −80°C. Analysis for effects on cell proliferation was then performed using the CyQUANT assay according to the manufacturer’s specifications. Experiments were repeated three times; the IC₅₀ for each cell line is shown.</p

Pharmacokinetics of KPT-335 in healthy dogs.

<p>Pharmacokinetics of KPT-335 in healthy dogs.</p

Constitutional and gastrointestinal toxicities.

<p>Constitutional and gastrointestinal toxicities.</p