Target | Traces | Population | Primary aim | Results |
---|---|---|---|---|
HER2 | 89Zr-trastuzumab | 14 pts, HER2 + mBC [25] | Dosing of tracer and timing of image acquisition | Relative uptake values in different organs, in tumor lesions and healthy tissue |
 |  | 56 pts HER2 + , mBC [29] | Investigate heterogeneity in HER2 status and evaluate therapy-predictive role for T-DM1 | Heterogeneity: 29% had negative PET, 46% heterogeneous uptake Predictive role: compared to RECIST 1.1, NPV and PPV for HER2-PET were 88% and 72% Combining HER2- and FDG-PET strongest NPV and PPV (both 100%) |
 |  | 11 pts, HER2- eBC [30] | Investigate whether HER2-PET can identify HER2-positive lesions in previously known HER2-negative tumors | Four patients with uptake on HER2-PET, of which one was confirmed as HER2 + on biopsy. The other 3 were considered as having false-positive HER2-PET results |
 | 64Cu-DOTA-trastuzumab | 8 pts, HER2 + mBC [31] | To detect and measure tumor uptake of trastuzumab | A cold dose of trastuzumab improves image quality High sensitivity of visualizing HER2 + lesions |
 |  | 18 pts mBC, 2 HER2-PET scans [32] | Compare HER2 status on PET (SUV) and biopsy (ISH) | PET uptake strongly related to pathological HER2 status, but with large interpatient variability |
 |  | 6 pts, HER2 + eBC or mBC [33] | Safety, distribution, internal dosimetry | Feasible for the identification of HER2-positive lesions. Acceptable dosimetry and pharmacologic safety |
 | 89Zr-pertuzumab | 6 pts, HER2 + mBC [26] | First in human | Safety, dosimetry, biodistribution and successful HER2-targeted imaging |
 |  | 24 pts mBC, HER2-neg primary tumor [34] | Evaluate HER2-positive lesions in pts with HER2-neg tumors | 6/24 pts with 89Zr-pert avid lesions, of which 3 have biopsy-confirmed HER2 positivity |
 |  | 9 pts, HER2- eBC [26] | Study heterogeneity in HER2 status in patients with HER2-negative primary tumor | 5 patients with HER2-uptake on PET; of these, two had biopsy-proven HER2-positive metastases. In the other three, tumor biopsy revealed HER2-negative status, and PET findings were considered false positive |
 | 68Ga-ABY-025 | 16 pts, HER2 + mBC [27] | Phase I/II aimed to study the effect of tracer peptide mass, test–retest variability and correlation of quantified uptake with histopathology | Correlation PET-SUV with IHC 0.91, no false-positive tracer uptake in HER2- lesions, SUV 5 times higher in HER2 + vs HER lesions, test–retest intra-class correlation r = 0.996 |
 | 68Ga-DOTA-F(ab’)2-trastuzumab | 16 pts mBC, HER2 + and HER2- [35] | First clinical evaluation to study safety, pharmacokinetics, biodistribution and dosimetry profile | Safety was confirmed, no unexpected findings related to dosimetry and distribution. Tumor uptake was seen in 4 out of 8 pts with HER2 + mBC |
 | 89Zr∙Df-HER2-Fab-PAS200 | 1 pt, HER2 + mBC [36] | First clinical study | Image acquisition after single dose, lesions could be detected 24 h after injection after appropriate blood clearance |
 | 68Ga-HER2-Nanobody | 20 pts with HER2 + eBC or mBC [37] | Phase 1 | Safe. Clear uptake in metastatic lesions, variable uptake in primary breast tumors |
 | 68Ga-NOTA-MAL-Cvs- ZHER2:342 | 2 pts mBC, one HER2 + and one HER2- [38] | Phase 1 | SUVmax HER2 + tumors 2.16 ± 0.27), SUVmax HER2- tumors 0.32 ± 0.05 |
PD-L1 | 89Zr-atezolizumab | 4 pts with mTNBC [39] | First In Human study | Tracer uptake in metastatic lesions in all mTNBC patients, no unexpected safety signals |
ER | 18F-FES | 90 pts with relapsed or de novo metastatic BC [40] | Assess the diagnostic accuracy and safety of 18F-FES-PET/CT to assess ER status | FES-PET positive: 36/36 biopsied with ER + tumor FES-PET negative: 11/49 biopsied with ER + tumor SUVmax 18F-FES vs Allred score r = 0.83, P < 0.0001 |
 |  | 19 pts with relapsed BC [41] | Investigate the utility of FES-PET to predict overall response to first-line endocrine therapy and validate previously defined cut-off SUVmean > 1.5 | FES SUVmean dynamic vs response to therapy after 6 months: partial response mean SUVmean 2.2 (1.8–3.0); stable disease SUVmean 3.6 (1.9–5.7); progressive disease SUVmean 1.9 (0.2–3.1) |
 |  | Meta-analysis of 12 trials [42] | Assess lesion-level agreement between ER IHC assays and qualitative assessment by 18F-FES-PET, primary analysis focused on metastatic lesions | Sensitivity metastatic lesions 0.78 (95% CI 0.65–0.88), specificity 0.98 (95% CI 0.65–1) |
 |  | Prospective trial 200 pts mBC [43] | ER expression in the biopsied metastasis was related to qualitative whole-body 18F-FES-PET evaluation and quantitative 18F-FES uptake in the corresponding metastasis | In 200 pts: sensitivity 95% (95% CI 89–97%), specificity 80% (95% CI 66–89%) |
 | 18F-4FMFES | Prospective trial 31 BC pts ER + tumors [44] | Compare diagnostic potential of 18F-4FMFES vs 18F-FES | 2.5-fold increase in metabolic stability of 18F-4FMFES over 18F-FES. SUVmax similar for both tracers, but improved diagnostic performance related to lower uptake in non-specific tissues for 18F-4FMFES |
PARP | 18F-FTT | Prospective trial in 13 BC pts with PET before and after PARPi treatment [45] | Evaluate in vivo visualization of PARP inhibitor pharmacodynamics, relate blockade of PARP1 expression in vitro or with repeated in vivo imaging | Nine of 13 pts underwent tumor resection and in vitro evaluation of 18F-FTT uptake with 125I-KX1 (an analog of 18F-FTT and uptake was blocked with PARPi Of the other 4 patients, 3 had 18F-FTT PET uptake pretreatment, and all had uptake blocked with treatment with a therapeutic PARPi as seen on a second 18F-FTT PET |
 |  | 30 pts with untreated stage I-IV BC [46] | Evaluate PARP1 expression in relation to tumor subtype and BRCA mutation status | Overlapping ranges of SUVmax between different tumor subtypes and between patients with and without germline BRCA mutations |