Physiological FAP-activation in a postpartum woman observed in oncological FAPI-PET/CT

Fibroblast activation protein (FAP) is a type II transmembrane serine protease overexpressed by cancer-associated fibroblasts [1]. However, high expression can also be observed in nonmalignant processes associated with tissue remodeling such as wound healing and diseases leading to fibrosis [2]. Our image presents a 29-year-old female patient with adenoid cystic carcinoma in the right parapharyngeal space with skull infiltration. The tumor was first diagnosed in 12/2018 and subsequently histologically confirmed with an initial classification of cT4 cN0 cM0. Within the scope of planning radiation therapy, a (Ga-FAPI-46) PET/CT was performed presenting a clear finding of the adenoid cystic carcinoma (a) with a SUVmax of 17.3, respectively. Surprisingly, the parenchyma in both breasts was well depicted with a SUVmax of 4.1 in the right and 3.5 in the left, respectively (b). The endometrium remarkably demonstrated a SUVmax of 25.7 as highlighted in c. Uptake in the thyroid (SUV 6.3) was also increased. We hypothesize that the presented high FAP-uptake in the hormone-sensitive organs such as breast parenchyma and endometrium is a physiological mechanism due to the fact that the presented patient is currently breastfeeding after giving birth 5 months ago. Post-partum thyroiditis is often asymptomatic, thus underdiagnosed and reflects chronic inflammation [3]. Breast parenchyma is characterized by low FAP expression in normal tissue, but high expression in breast cancer [4, 5]. Furthermore, the density of breast and fibro-glandular tissue depends on dynamic physiologic processes based on endogenous and exogenous hormonal fluctuations. During lactation, the cessation of progesterone secretion leads to the release of prolactin, enabling cell vacuolization and secretory changes resulting in the production of milk [6]. Therefore, an increased parenchymal breast density can be seen [7] with an increased FAP expression as a functional correlate. This case demonstrates that a physiologic increase in FAP expression in hormone-sensitive organs such as the breasts and uterus may occur in the post-pregnancy period and breastfeeding.

Fibroblast activation protein (FAP) is a type II transmembrane serine protease overexpressed by cancer-associated fibroblasts [1]. However, high expression can also be observed in nonmalignant processes associated with tissue remodeling such as wound healing and diseases leading to fibrosis [2].
Our image presents a 29-year-old female patient with adenoid cystic carcinoma in the right parapharyngeal space with skull infiltration. The tumor was first diagnosed in 12/2018 and subsequently histologically confirmed with an initial classification of cT4 cN0 cM0. Within the scope of planning radiation therapy, a ( 68 Ga-FAPI-46) PET/CT was performed presenting a clear finding of the adenoid cystic carcinoma (a) with a SUVmax of 17.3, respectively. Surprisingly, the parenchyma in both breasts was well depicted with a SUVmax of 4.1 in the right and 3.5 in the left, respectively (b). The endometrium remarkably demonstrated a SUVmax of 25.7 as highlighted in c. Uptake in the thyroid (SUV 6.3) was also increased.
We hypothesize that the presented high FAP-uptake in the hormone-sensitive organs such as breast parenchyma and endometrium is a physiological mechanism due to the fact that the presented patient is currently breastfeeding after giving birth 5 months ago. Post-partum thyroiditis is often asymptomatic, thus underdiagnosed and reflects chronic inflammation [3]. Breast parenchyma is characterized by low FAP expression in normal tissue, but high expression in breast cancer [4,5]. Furthermore, the density of breast and fibro-glandular tissue depends on dynamic physiologic processes based on endogenous and exogenous hormonal fluctuations. During lactation, the cessation of progesterone secretion leads to the release of prolactin, enabling cell vacuolization and secretory changes resulting in the production of milk [6]. Therefore, an increased parenchymal breast density can be seen [7] with an increased FAP expression as a functional correlate.
This case demonstrates that a physiologic increase in FAP expression in hormone-sensitive organs such as the breasts and uterus may occur in the post-pregnancy period and breastfeeding.
Funding Open Access funding enabled and organized by Projekt DEAL.

Compliance with ethical standards
Ethics approval and consent to participate The radiopharmaceutical was used on an individual patient basis according to German Pharmaceuticals Act §13(2b). The patient gave written informed consent to receive the novel diagnostics and permitted anonymized publication of related medical data. The ethical committee of Heidelberg University approved this retrospective evaluation to be in accordance with the Helsinki declaration. For case reports from clinical practice, no trial registration is required.
Conflict of interest UH, CK, and FLG have a patent application for quinolone-based FAP-targeting agents for imaging and therapy in nuclear medicine. UH, CK, and FLG have shares of iTheranostics.
FLG is a medical advisor for ABX Advanced Biochemical Compound and Telix Pharmaceuticals. SA received grants from Accuray International Sàrl, Merck Serono GmbH, Novocure GmbH, MSD, and Astra Zeneca outside the submitted work. S.A. Novocure GmbH, Actinium Pharmaceuticals, Telix Pharmaceuticals shareholding.
SAK reports grants from Viewray Inc., outside the submitted work.
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