{Reference Type}: Journal Article {Title}: Comparison of an Affibody-based Molecular Probe and 18F-FDG for Detecting HER2-Positive Breast Cancer at PET/CT. {Author}: Guo X;Zhou N;Liu J;Ding J;Liu T;Song G;Zhu H;Yang Z; {Journal}: Radiology {Volume}: 311 {Issue}: 3 {Year}: 2024 Jun {Factor}: 29.146 {DOI}: 10.1148/radiol.232209 {Abstract}: Background Human epidermal growth factor receptor 2 (HER2) affibody-based tracers could be an alternative to nonspecific radiotracers for noninvasive detection of HER2 expression in breast cancer lesions at PET/CT. Purpose To compare an affibody-based tracer, Al18F-NOTA-HER2-BCH, and fluorine 18 (18F) fluorodeoxyglucose (FDG) for detecting HER2-positive breast cancer lesions on PET/CT images. Materials and Methods In this prospective study conducted from June 2020 to July 2023, participants with HER2-positive breast cancer underwent both Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT. HER2 positivity was confirmed with pathologic assessment (immunohistochemistry test results of 3+, or 2+ followed by fluorescence in situ hybridization, indicated HER2 amplification). Two independent readers visually assessed the uptake of tracers on images. Lesion uptake was quantified using the maximum standardized uptake value (SUVmax) and target to background ratio (TBR) and compared using a general linear mixed model. Results A total of 42 participants (mean age, 56.3 years ± 10.1 [SD]; 41 female) with HER2-positive breast cancer were included; 42 (100%) had tumors that were detected with Al18F-NOTA-HER2-BCH PET/CT and 40 (95.2%) had tumors detected with 18F-FDG PET/CT. Primary tumors in two of 21 participants, lymph node metastases in four of 21 participants, bone metastases in four of 15 participants, and liver metastases in three of nine participants were visualized only with Al18F-NOTA-HER2-BCH. Lung metastasis in one of nine participants was visualized only with 18F-FDG. Al18F-NOTA-HER2-BCH enabled depiction of more suspected HER2-positive primary tumors (26 vs 21) and lymph node (170 vs 130), bone (92 vs 66), and liver (55 vs 27) metastases than 18F-FDG. The SUVmax and TBR values of primary tumors and lymph node, bone, and liver metastases were all higher on Al18F-NOTA-HER2-BCH images than on 18F-FDG images (median SUVmax range, 10.4-13.5 vs 3.4-6.2; P value range, <.001 to .02; median TBR range, 2.7-17.6 vs 1.2-7.8; P value range, <.001 to .001). No evidence of differences in the SUVmax and TBR for chest wall or lung metastases was observed between Al18F-NOTA-HER2-BCH and 18F-FDG (P value range, .06 to .53). Conclusion PET/CT with the affibody-based tracer Al18F-NOTA-HER2-BCH enabled detection of more primary lesions and lymph node, bone, and liver metastases than PET/CT using 18F-FDG. ClinicalTrials.gov Identifier: NCT04547309 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ulaner in this issue.