Simultaneous FAPI PET/MRI Targeting the Fibroblast-Activation Protein for Breast Cancer

Abstract

Integrated PET/MRI is a promising modality for breast assessment. The most frequently used tracer, fluorine 18 ( 18 F) fluorodeoxyglucose (FDG), is applied for whole-body staging in advanced breast cancer but has limited accuracy in evaluating primary breast lesions. The fibroblast-activation protein (FAP) is abundantly expressed in invasive breast cancer. FAP-directed PET tracers have recently become available, but results in primary breast tumors remain lacking.Purpose: To evaluate the use of FAP inhibitor (FAPI) breast PET/MRI in assessing breast lesions and of FAPI whole-body scanning for lymph node (LN) and distant staging using the ligand gallium 68 ( 68 Ga)-FAPI-46. Materials and Methods:In women with histologically confirmed invasive breast cancer, all primary 68 Ga-FAPI-46 breast and wholebody PET/MRI and PET/CT examinations conducted at the authors' center between October 2019 and December 2020 were retrospectively analyzed. MRI lesion characteristics and standardized uptake values (SUVs) were quantified with dedicated software. Mann-Whitney U tests were used to compare tumor SUVs across different tumor types. The Pearson correlation coefficient was calculated between SUV and measures of MRI morphologic characteristics.Results: Nineteen women (mean age, 49 years 6 9 [standard deviation]) were evaluated-18 to complement initial staging and one for restaging after therapy for distant metastases. Strong tracer accumulation was observed in all 18 untreated primary breast malignancies (mean maximum SUV [SUV max ] = 13.9 [range, 7.9-29.9]; median lesion diameter = 26 mm [range, 9-155 mm]), resulting in clear tumor delineation across different gradings, receptors, and histologic types. All preoperatively verified LN metastases in 13 women showed strong tracer accumulation (mean SUV max = 12.2 [range, 3.3-22.4]; mean diameter = 21 mm [range, 14-35 mm]).Tracer uptake established or supported extra-axillary LN involvement in seven women and affected therapy decisions in three women. Conclusion:This retrospective analysis indicates use of 68 Ga fibroblast-activation protein inhibitor tracers for breast cancer diagnosis and staging.

Translational imaging of the fibroblast activation protein (FAP) using the new ligand [68Ga]Ga-OncoFAP-DOTAGA

“…We compared the biodistribution and tumor binding of 68 Ga-OncoFAP to a previously published study sample of 19 patients with breast cancer scanned with the FAP ligand 68 Ga-FAPI-46 (Table 3 , Fig. 5 ) [ 10 ]. Patient and acquisition characteristics of the two samples were largely identical except for a higher fraction of males and a broader spectrum of underlying malignancies in the patients scanned with 68 Ga-OncoFAP.…”

“…68 Ga-OncoFAP demonstrated higher uptake in the uterus and pancreas, whereas 68 Ga-FAPI-46 demonstrated higher uptake in the liver and spleen. However, following Bonferroni correction for multiple testing results ( p -value threshold for significance indicated by * for patient characterics, imaging characteristics and SUV max of targeted lesions of p < .013, and for SUV mean in remaining organs of p < .006), only the hepatic uptake remained statistically different Measurement 68 Ga-OncoFAP mean ± SD ( n = 12, if not specified) 68 Ga-FAPI-46 mean ± SD ( n = 19, if not specified) [ 10 ] p -value Age 52 ± 14 49 ± 9 .41 Female/male 8/4 19/0 .009* Weight 74.9 ± 12.3 71.2 ± 14.4 .28 Breast cancer/other disease 8/4 19/0 .009* Whole-body PET/CT/PET/MRI 7/5 9/10 .57 Activity (MBq) 163.3 ± 49.5 148.8 ± 47.9 .60 Supine whole-body imaging (min p.i.) 64 ± 18 79 ± 18 .06 Prone breast imaging (min p.i.)…”

“…68 Ga-FAPI-46 was synthesized as described previously [ 10 ]. FAPI-46 precursor for preclinical and clinical imaging was kindly provided under a MTA by U. Haberkorn (Heidelberg, Germany).…”

“…Patient were scanned in supine whole-body PET/CT (mCT, Siemens Healthineers) or PET/MRI (mMR, Siemens Healthineers) ~ 1 h p.i. as described previously [ 10 ]. Breast cancer patients additionally received prone breast PET/MRI before the whole-body scan ~ 30 min p.i., and subsequent diagnostic contrast-enhanced CT or MRI was added according to the specific clinical demand; see Table 3 for details.…”

“…As of now, a growing body of clinical studies has established a high versatility of FAPI-PET to detect the spread of a wide range of cancers. Importantly, FAPI-PET seems to be able to fill clinically urging shortcomings of 18 F-FDG, for example in pancreatic cancer [ 7 ], primary liver tumors [ 8 ], gastric and bowel cancer [ 9 ], and breast cancer [ 10 ].…”