Positron emission tomography (PET) is a commonly used imaging technique in human medicine to help manage and evaluate the oncological status of organs (1–4). ¹⁸F-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) is used as a radiotracer to help visualize the glucose metabolic rate in tissues (5, 6). This is because ¹⁸F-FDG is similar to glucose and migrates into the cells through glucose transporter proteins. However, unlike glucose, ¹⁸F-FDG becomes trapped within the cells because it is not converted into energy through glycolytic pathways (7–10). Generally, most malignant tumor cells have higher glucose metabolic activity than normal tissues (8, 10, 11). Consequently, PET has been utilized to detect malignancy and metastasis of tissues. PET scans operate by identifying malignant cells through the measurement of the uptake of 18F-FDG in a certain area, often before noticeable anatomical changes (12). Because of relatively low spatial resolution of PET, PET combined with computed tomography (PET/CT), which has a relatively lower spatial resolution, is an advanced imaging technique that helps provide superior anatomical information and maps the glucose metabolism of tissues through automatic image fusion (7, 13, 14).

PET/CT scans in human medicine have been widely utilized as a diagnostic tool across numerous fields. In cardiology, PET/CT scans serve as a clinically important diagnostic tool for characterizing the myocardial tissue viability of patients with coronary artery diseases (15). These scans can also be used to visualize non-tumoral bone and soft tissue disorders. This makes it a useful tool for the evaluation of orthopedic and rheumatologic diseases, allowing for more precise diagnosis and treatment planning (16). Furthermore, in neurologic medicine, PET/CT is a sophisticated technique that presents high spatial resolution and integrates functional data with morphological information. The information from the detailed images of PET/CT not only shows the precise location of abnormalities but also provides insights into the metabolic activity of the tissues. This information also helps in the diagnosis and management of CNS disorders (17). Additionally, there is an extensive research in human medicine on the degree of physiological ¹⁸F-FDG uptake of variable normal and tumorous tissues based on PET/CT (18, 19). Malignancy and functional statuses of the tissues have been identified by the measurement of standardized uptake values (SUVs) (11). Similar to the physiological SUVs in human tissues, the physiological SUVs of ¹⁸F-FDG in normal canine and feline tissues were reported previously (20, 21). However, no studies have been conducted on the physiological range of ¹⁸F-FDG SUVs in the reproductive tissues of dog ovaries.

This study aimed to investigate the ¹⁸F-FDG SUV uptake range of normal canine ovaries by examining the SUVs of seven dogs. This is the first article that demonstrated the physiological ¹⁸F-FDG uptake range of normal ovaries in dogs.

The dogs showed stable vital signs such as no abnormalities in the heart rate, respiratory rate, blood pressure, or blood glucose during general anesthesia and acquisition of the PET/CT scan images. The range of post-scan glucose concentration in all dogs was 82.3 ± 8.2 mg/dL (mean ± SD). The dogs included were of small to medium size [body weight = 9.8 ± 3.6 kg (mean ± SD)] and of variable age [6.1 ± 6 years old (mean ± SD)] from four breeds. All dogs had normal ovaries based on CT and were fused with the PET after verifying the location and size of the ovaries to confirm the ¹⁸F-FDG uptake (Figure 1).

The characteristics and SUV max and mean values of ¹⁸F-FDG of the seven dogs are shown in Table 1. The ¹⁸F-FDG uptake of transverse, sagittal, and coronal image planes of bilateral ovaries was measured to quantitatively evaluate the amount of ¹⁸F-FDG. The mean and standard deviations with a 95% confidence interval for SUV maximum and mean within ROIs in the left, right, and bilateral ovaries are shown in Table 2.

The SUV max and mean values of the left ovary were 1.47 ± 0.13 and 1.21 ± 0.15 (mean ± SD), respectively. Similarly, the SUV max and mean values of the right ovary were 1.43 ± 0.30 and 1.17 ± 0.17 (mean ± SD), respectively. There was no significant difference between the SUV max and mean values of the left and right ovaries. Comprehensively, SUV max and mean values of the bilateral ovaries were 1.45 ± 0.22 and 1.19 ± 0.16 (mean ± SD), respectively. Overall, these SUV values could be considered the physiological range of ¹⁸F-FDG of normal canine ovaries.

There are numerous studies in human medicine that evaluate the physiological ¹⁸F-FDG uptake in the reproductive organs based on PET/CT scans to distinguish between physiological processes and pathological conditions (22, 23). One PET/CT scan study on normal testis helped elucidate the normal physiological patterns of the ¹⁸F-FDG uptake and showed a correlation between the testicular ¹⁸F-FDG uptake, testicular size, and patient’s age (22). These baseline ranges can be used to differentiate the normal testicular function and the pathological change. In addition to studies investigating the uptake of ¹⁸F-FDG in normal testes and its correlation with testicular size, there has also been research on the relationship between testicular health and parameters such as total sperm count, sperm concentration, and motility (23). Research on ¹⁸F-FDG uptake in PET/CT scans has been extensive not only for male reproductive organs but also for female reproductive organs. In studies examining the ¹⁸F-FDG uptake in the human endometrium, the range of the ¹⁸F-FDG uptake in pre-menopausal women was established based on the four phases of the menstrual cycle including menstrual, ovulatory, proliferative, and secretory phases (24). Research has also been conducted on the physiological uptake of the ¹⁸F-FDG in the fallopian tubes, also known as uterine tubes. The uptake of ¹⁸F-FDG is more prominent in women during the mid-menstrual cycle. These findings suggest that the uptake of ¹⁸F-FDG in the fallopian tubes is influenced by ovarian hormones, particularly estrogen (25).

In this study, the physiological ¹⁸F-FDG uptake range on PET/CT scans of normal dog ovaries was established in seven dogs. In human medicine, in contrast to veterinary medicine, there are several reports on the ¹⁸F-FDG uptake of normal ovaries. One of the research studies has been conducted according to the phases of the menstrual cycle. The SUV of normal ovaries was 3.9 ± 0.7 in 26 pre-menopausal women during the follicular to luteal phase of the menstrual cycle. Furthermore, this study also identified that, in post-menopausal women, there was no observable ¹⁸F-FDG uptake in the ovaries and uterus (26). Compared to the SUVs of normal ovaries in the dogs identified in this study, the SUVs of human ovaries are higher. Based on these results, it can be inferred that there is a higher glucose metabolism in human ovaries compared to dog ovaries. Similarly, studies have found that the ¹⁸F-FDG uptake in the normal brains of dogs is measured to be lower than that in the normal human brains (21, 27). However, in the case of animals, a general anesthetic process is required for PET/CT scans, which is likely due to the glucose metabolic suppression during anesthesia (28).

The physiological range of the ¹⁸F-FDG uptake in the normal ovaries in dogs, as determined through PET/CT scans, can be effectively utilized in the assessment of patients with ovarian tumors. In PET/CT imaging, a higher ¹⁸F-FDG uptake indicates an increased metabolic activity as observed in many cancerous cells (7, 8). In patients with suspected ovarian tumors, PET/CT scans can help in differentiating between benign and malignant lesions by comparing their ¹⁸F-FDG uptake to the physiological range observed in normal ovaries before anatomical changes (2, 4). Tumors with ¹⁸F-FDG uptake significantly higher than the normal range are more likely to be malignant, while those within or close to the normal range may indicate benign tumors (10, 12). This method is particularly useful in the staging of ovarian cancer, planning treatment strategies, monitoring the effectiveness of therapy, and detecting recurrence (12). In human medicine, some studies have utilized ¹⁸F-FDG uptake in PET/CT imaging to assess the malignancy and metastasis of ovarian tumors (29–31). In addition to identifying the presence of tumors, a study conducted on ovarian tumor patients compared the SUV max to distinguish between borderline ovarian tumors and malignant ovarian tumors, which was found to be 2.9 ± 1.5 and 6.6 ± 2.9 (mean ± SD) (32). In veterinary medicine, ovarian remnant syndrome refers to a condition where the ovarian tissue remains in the body after ovariohysterectomy (33). There are several cases where these remnants can undergo tumorous changes, potentially leading to malignancy at an early stage (33, 34). Therefore, it has been established that, following a PET/CT scan, the determined ¹⁸F-FDG uptake in the ovaries can be utilized as a crucial diagnostic tool for identifying malignant ovarian lesions. The ability to quantify ¹⁸F-FDG uptake allows for a more precise assessment of the ovarian tissue.

There are some limitations of this study. First, this study was conducted with a small sample size for physiological uptake. Due to the small sample size, there is a potential for an increased margin of error and limited generalizability. Further studies using larger sample sizes could enhance the reliability of the study. Second, there are various factors that can influence the measurement of SUV calculation. Those factors include the size of ROIs, tissue or organ size, blood glucose concentration of the sample, and injection time of ¹⁸F-FDG (35). Third, there is a lack of information on the relationship between the ¹⁸F-FDG uptake and the physiological estrus cycle of dogs. In human medicine, some studies suggest that the menstrual status of pre-menopausal women can affect the physiological uptake of ¹⁸F-FDG on PET/CT scans (24, 26, 36). Furthermore, in post-menopausal women, normal ovaries demonstrate significantly less ¹⁸F-FDG uptake compared to those in pre-menopausal women (24). Additional research on ¹⁸F-FDG uptake throughout the canine estrous cycle will be helpful in the physiological ¹⁸F-FDG uptake range for normal ovaries. Finally, another limitation is that the ¹⁸F-FDG uptake on PET/CT can also be increased due to inflammatory or infected tissues and organs, which can lead to false-positive results (37).

In conclusion, this is the first study to investigate the physiological ¹⁸F-FDG uptake range of normal dog ovaries based on PET/CT scans. The ¹⁸F-FDG uptake range contributes to the baseline knowledge, which is necessary for the accurate interpretation of PET/CT scans in veterinary oncology, and provides a reference point to help distinguish physiological uptake from malignant transformation in canine ovaries. Therefore, malignant lesions of the ovary can thus be detected before structural changes, enabling the early diagnosis and assessment of patient prognosis.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.

The animal studies were approved by the Institutional Animal Care and Use Committee (CBNUA-2188-23-02). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent was obtained from the owners for the participation of their animals in this study.

JC: Conceptualization, Data curation, Formal analysis, Writing – original draft. YC: Conceptualization, Data curation, Formal analysis, Writing – review & editing. B-TK: Writing – review & editing. SL: Conceptualization, Formal analysis, Supervision, Writing – original draft.