A new animal model for the imaging of melanoma: correlation of FDG PET with clinical outcome, macroscopic aspect and histological classification in Melanoblastoma-bearing Libechov Minipigs

Abstract

The aim of this study was to evaluate the Melanoblastoma-bearing Libechov Minipigs (MeLiM) as an animal model of melanoma for in vivo imaging. Serial whole-body 2-deoxy-2-[(18)F]fluoro- d-glucose positron emission tomography (FDG PET) scans were conducted on five MeLiM. In order to explore different clinical stages of the tumoural lesions, each animal was scanned two to four times, at intervals of 30-155 days. PET images were analysed by a semiquantitative method based on the tumour to muscle metabolic ratio. Histology was performed on biopsies taken between or after the scans and the histological grading of the tumours was compared with the FDG uptake. The overall sensitivity of FDG PET for the detection of cutaneous melanoma was 75%; 62.5% of involved lymph nodes were positive. Sensitivity was better for tumours with vertical growth than for flat lesions. FDG PET did not detect tumours with epidermal involvement only, nor did it detect small metastatic foci. The metabolic ratio was correlated with the evolution of the melanoma. FDG PET is effective in the staging of cutaneous melanoma and the follow-up of tumoural extension and regression in Melanoblastoma-bearing Libechov Minipigs. The results obtained in this animal model correlate well with those described in human melanoma. Accordingly, this model may be useful in testing new tracers specific for melanoma and in helping to detect molecules expressed early during tumoural regression.

In Vivo Follow-up of Rat Tumor Models with 2-Deoxy-2-[F-18]fluoro-d-glucose/Dual-Head Coincidence Gamma Camera Imaging

“…We also found that our imaging technique was a sensitive device for detecting metastasis larger than 5 mm. The in vivo monitoring of animal models with functional imaging can define disease progression or regression with dedicated PET [13] but also with DHC, when provided with a longer uptake period, as shown in our study. Various therapies modify metabolic pathways and thus FDG uptake is different prior to and after treatment.…”

“…This may be explained by the relative lack of sensitivity and resolution of this technique, compared to dedicated PET scanners or, even more, to animal dedicated PET cameras. Animal PET scanners have a spatial resolution range of about 2 mm [10,11], while dedicated PET have a spatial resolution range of about 4Y6 mm [12,13] and DHC have a resolution of about 5 to 8 mm [14Y16]. Dedicated PET cameras and animal PET cameras also have a better detection limit because their sensitivity (in air with a line source) is 150 times greater in 3-D and 25 times greater in 2-D than DHC [15].…”

“…More demanding than SUV, the Patlak slope is obtained with dynamic imaging and requires a tumor timeYactivity curve and an arterial input function of the FDG blood concentration. SUV and Patlack slope methods were found to depend heavily on animal weight in minipigs [13]. Due to rapid weight changes, these methods are not suitable for the follow-up of small animals such rodents.…”

Animal models and molecular imaging tools to investigate lymph node metastases

“…Immunodeficient murine models allow for the study of human and murine melanomas in an immunological naive background [17–19]. In addition to providing a large animal model of LNM, spontaneous swine melanoma models are used to examine practical limitations of current imaging techniques [20–22]. …”

Inheritance of malignant melanoma in the melim strain of miniature pigs

“…The MeLiM minipigs are a very suitable animal model for human melanoma due to numerous histopathological (Boisgard et al, 2003;VincentNaulleau et al, 2004) and biochemical similarities (Borovansky et al, 2003). Comparing the melanomas in the MeLiM strain and the Sinclair strain or the Munich Troll line, some resemblance exists, such as the occurrence of melanoma at birth and multiple gene inheritance Horak et al, 1999).…”