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Tracer type No. of ongoing trials Target 18F-FES 11 ER 18F-FLT 6 ENT1/TK1 18F-fluorocholine 1 ChK-α 18F-fluoro furanyl norprogesterone 1 Progesterone receptor 18F-fluoromisonidazole 1 Hypoxia 18F-fluoroethoxy-5-methylbenzamide 2 Sig-2R 18F-fluorodihydrotestosterone 1 AR 18F-sodium fluoride 3 Bone formation 18F-fluciclatide 1 Αvβ3 18F-FMAU 1 DNA synthesis 18F-fluoroazomycin-arabinoside 1 18F-EF5 1 EF5 18F-fluoride 1 18F-paclitaxel 2 Tubulin 18F-fluorocyclobutanecarboxylic acid 3 18F-RGD-K5 (flotegatide) 1 Αvβ3 18F-fluorobenzyl triphenylphosphonium 1 Perfusion 11C-lapatinib 1 EGFR and HER2 11C-choline 1 ChK-α 89Zr-trastuzumab 6 HER2 89Zr-bevacizumab 3 VEGF-A 111In-trastuzumab 1 HER2 68Ga-ABY-025 2 HER2 68Ga-IMP-288 1 CEA 68Ga-NOTA-NFB 1 CXCR4 64Cu-DOTA-trastuzumab 3 HER2 64Cu-DOTA-AE105 1 Urokinase plasminogen activator receptor 64Cu-anti-CEA 1 CEA 2-deoxy-d-glucose 1 GLUT-1/HKII ONT-10 1 MUC1 lipid A Nonspecified 17 ENT1/TK1 = equilibrative nucleoside transporter 1/thymidine kinase 1; ChK-α = choline kinase-α; Sig-2R = σ-receptor subtype 2; AR = androgen receptor; Αvβ3 = vitronectin receptor integrin α-V and integrin β-3; 18F-FMAU = 18F-1-(2′-deoxy-2′-fluoro-d-arabinofuranosyl)thymine; EF5 = 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide; RGD-K5 = 2-((2S,5R,8S,11S)-5-benzyl-8-(4-((2S,3R,4R,5R,6S)-6-((2-(4-(3-18F-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)butyl)-11-(3-guanidinopropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaazacyclopentadecan-2-yl)acetic acid; EGFR = endothelial growth factor receptor; VEGF-A = vascular endothelial growth factor A; ABY-025 = maleimide-DOTA-Cys61-ZHER2; CEA = carcinoembryonic antigen; NOTA-NFB = p-SCN-Bn-NOTA with T140-NFB; CXCR4 = chemokine (C-X-C motif) receptor 4; AE105 = urokinase plasminogen activator receptor antagonist; GLUT-1/HKII = glucose transporter 1/hexokinase 2; ONT-10 = oncothyreon vaccin 10; MUC1 = mucin 1.
No. of patients Study aim(s) Results Reference 18 Determine whether early changes in 18F-FLT PET can predict benefit from docetaxel Docetaxel decreased 18F-FLT uptake; early reduction in tumor SUV correlated with tumor size changes after 3 cycles and predicted midtherapy response 58 13 Define objective criteria for 18F-FLT response and examine whether 18F-FLT PET can be used to quantify early response of stage II–IV breast cancer to FEC Clinical response at day 60 was related to reduction in 18F-FLT uptake at 1 wk; decreases in Ki-67 and SUV90 at 1 wk discriminated between clinical response and stable disease 59 15 Evaluate whether 18F-FLT PET can predict final postoperative histopathologic response in primary locally advanced breast cancer after 1 cycle of NAC Potential utility for early monitoring of response 60 28 Investigate diagnostic performance of 18F-FLT PET in women with suspect breast findings on conventional imaging SUV of malignant lesions was higher than that of benign lesions 61 30 Investigate quantitative methods of tumor proliferation with 18F-FLT PET before and after single bevacizumab administration and correlate 18F-FLT uptake with Ki-67 18F-FLT uptake decreased after treatment 62 20 Assess feasibility of 18F-FLT PET/CT for predicting response to NAC and for comparing baseline 18F-FLT with Ki-67 No association of baseline, postchemotherapy, or change in SUVmax with pathologic response to NAC; prechemotherapy Ki-67 correlated with SUVmax 63 15 Validate approach to quantify 18F-FLT PET data in stage II–IV breast cancer patients and study whether 18F-FLT PET can predict early treatment response Differences before and after therapy in mean voxel uptake in tumor did not allow complete responder/nonresponder classification 64 12 Evaluate use of 18F-FLT PET for diagnosis of breast cancer Totals of 13/14 primary tumors and 7/8 histologically proven lymph node metastases showed uptake 65 14 Examine side-by-side 18F-FDG imaging and 18F-FLT imaging for monitoring and predicting chemotherapy response Mean change in 18F-FLT uptake correlated with late changes in CA27.29 and CT response 66 10 Study feasibility of 18F-FLT PET for breast cancer visualization Totals of 8/10 primary tumors and 2/7 axillary lymph node metastases showed uptake 67 FEC = 5-fluorouracil–epirubicin–cyclophosphamide; Ki-67 = cellular marker for proliferation; NAC = neoadjuvant chemotherapy.
No. of patients Study aim(s) Results Reference 47 Quantify tumor 18F-FES uptake as predictor of endocrine therapy response Absence of uptake predicted failure of endocrine therapy 38 19 Investigate utility of 18F-FES PET for predicting overall response to first-line endocrine therapy in MBC Low or absent 18F-FES uptake correlated with lack of ER expression 39 11 Assess serial 18F-FES PET and 18F-FDG PET for predicting response to tamoxifen Increase in 18F-FDG uptake and decrease in 18F-FES uptake after start of tamoxifen predicted response 40 30 Measure changes in 18F-FES uptake with aromatase inhibitors, tamoxifen, or fulvestrant No effect with aromatase inhibitors; ∼55% decrease with tamoxifen or fulvestrant 41 40 Assess serial 18F-FES PET and 18F-FDG PET for predicting response to tamoxifen Increase in 18F-FDG uptake and decrease in 18F-FES uptake after start of tamoxifen predicted response 42 16 Evaluate whether 500 mg of fulvestrant optimally abolishes ER availability in tumor 18F-FES PET showed residual ER availability during fulvestrant therapy in 38% of patients; this finding was associated with early progression 43 59 Investigate whether 18F-FES PET and serial 18F-FDG PET predict response to endocrine therapy Baseline 18F-FES uptake and metabolic flare after estradiol challenge predicted treatment response 68 17 Assess correlation between 18F-FES uptake and IHC Good correlation for ER was observed 69 53 Compare 18F-FES PET with 18F-FDG PET and IHC 18F-FES PET showed 88% agreement with IHC and provided information not obtained with 18F-FDG PET 70 91 Measure variability in 18F-FES uptake between and within patients Substantial variations in 18F-FES uptake between and within patients were observed 71 13 Assess feasibility of 18F-FES PET for detecting primary ER-positive breast cancer lesions and correlation with in vitro status Focal uptake of 18F-FES was seen in all tumors; uptake correlated well with in vitro assays 72 239 Assess correlation between 18F-FES PET and clinical and laboratory data, effects of previous treatments, and 18F-FES metabolism 18F-FES uptake correlated positively with BMI and inversely with plasma sex hormone–binding globulin levels and binding capacity 73 18 Assess clinical value of dual PET/CT tracers 18F-FES and 18F-FDG in predicting response to NAC 18F-FES PET/CT may be feasible for predicting response to NAC 74 32 Investigate heterogeneity of ER expression among tumor sites with 18F-FES PET 18F-FES uptake and 18F-FDG uptake varied greatly within and among patients; 18F-FES PET/CT showed heterogeneous ER expression 75 48 Correlate 18F-FES PET with ER expression in patients with primary, operable breast cancer 18F-FES PET SUV correlated with IHC ER expression; size of primary tumor was associated with 18F-FES PET SUV 76 33 Evaluate clinical value of 18F-FES PET/CT in assisting with individualized treatment decisions for ER-positive breast cancer patients Treatment plan was changed in 48.5% of cases on basis of 18F-FES PET/CT results 53 ICH = immunohistochemistry; BMI=body mass index; NAC = neoadjuvant chemotherapy.
Trial identifier No. of patients Primary outcome measures Secondary outcome measures NCT02409316 75 Evaluate 18F-FES PET/CT uptake as predictor of PFS in patients who had recurrent cancer refractory to endocrine therapy or MBC and were starting new therapy regimen including endocrine therapy Correlate 18F-FES uptake, IHC, and experimental pathology markers
Evaluate utility of combined 18F-FES PET/CT and 18F-FDG PET/CT in identifying heterogeneity of ER expression and functionality in MBC
Compare 18F-FES uptake at baseline and progression in patients receiving additional endocrine therapy
Correlate 18F-FES uptake with CTCs and ratio of ER+ to ER− CTCsNCT01986569 94 Lesion-level 18F-FES PET interpretation and reference IHC testing in stage IV MBC patients Not provided NCT02398773 99 Negative predictive value of 18F-FES uptake for clinical benefit in ER+, HER2− MBC patients Evaluate relationship between 18F-FES uptake and semiquantitative ER measures
18F-FES SUVmax of <1.5 as optimal cutoff point for predicting PFS
Percentage of eligible patients for whom biopsy is not feasible, i.e., predictive accuracy of 18F-FES PET/CT for PFS; significance of 18F-FES PET measures in predicting progressive disease or clinical benefitNCT02149173 80 Change in 18F-FES SUV in ER+ MBC patients undergoing endocrine therapy
Proportion of patients experiencing threshold as percentage changeSafety profile of 18F-FES PET
Correlate 18F-FES PET uptake measures with histopathologic assays and microenvironment studies of biopsy specimensNCT01988324 20 Concordance between PET results and IHC of biopsied lesions from ER+ MBC patients Numbers of lesions detected on PET vs. CT and bone scanning
Inter- and intrapatient variations
Interobserver variationNCT01627704 72 Compare response rate after 6 mo of endocrine treatment in MBC patients with 18F-FES uptake in metastatic lesions Determine whether 18F-FES PET/CT is able to detect metastases that are not visible on 18F-FDG PET/CT; determine nature of discordant 18F-FES and 18F-FDG foci; validate and improve interpretation criteria for 18F-FES PET/CT; confirm tolerance NCT00816582 100 Rate of clinical benefit of fulvestrant in MBC patients Not provided NCT00647790 79 Preoperatively evaluate ER status of breast cancer on PET imaging in primary breast cancer patients undergoing surgery Correlate ER positivity on PET imaging and conventional IHC NCT01153672 8 Determine rate of clinical benefit for patients treated with cycles of 2 wk of vorinostat and then 6 wk of aromatase inhibitor Change in 18F-FES SUV after 2 and 8 wk
Change in 18F-FDG SUV after 2 and 8 wkNCT01275859 25 Evaluate rate of pathologic complete response to lapatinib plus letrozole in neoadjuvant setting Correlation of 18F-FES PET with biologic and imaging predictors of response
Evaluate diagnostic value of 18F-FES PET SUV for predicting response to therapyNCT01957332 200 Evaluate clinical utility of experimental PET scans in setting of MBC at first presentation Correlation PET scans with (progression-free) survival
Cost-effectiveness of molecular imaging
Quality of lifePFS = progression-free survival; IHC = immunohistochemistry; CTCs = circulating tumor cells; ER+ = estrogen receptor–positive; ER− = estrogen receptor–negative.
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- Article
- Abstract
- SEARCH STRATEGY
- TRANSITION OF TRACERS FROM PRECLINICAL EVALUATION TO FIRST-IN-HUMAN STUDIES
- ROLE OF 18F-FDG PET IN STANDARD BREAST CANCER CARE
- 18F-FLT PET IN BREAST CANCER
- 18F-FES PET IN BREAST CANCER
- MULTICENTER STUDIES AND REPRODUCIBILITY OF RESULTS
- TRIAL DESIGNS TO PROVE ROLES OF NEW MOLECULAR IMAGING METHODS IN CLINICAL SETTINGS
- CONCLUSION
- DISCLOSURE
- Footnotes
- REFERENCES
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