PET/CT with Fibroblast Activation Protein Inhibitors in Breast Cancer: Diagnostic and Theranostic Application—A Literature Review
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Literature Search
2.2. Inclusion and Exclusion Criteria and Data Analysis
3. Results
3.1. Literature Research
3.2. Diagnostic PET Imaging
3.2.1. Clinical and Methodological Studies’ Characteristics
3.2.2. 68Ga-FAPI PET Diagnostic Performance: Primary BC Lesion and Comparison with 18F-FDG
3.2.3. Physiological 68Ga-FAPI Breast Uptake
3.2.4. Effect of Hormonal Status on 68Ga-FAPI Breast Uptake
3.2.5. 68Ga-FAPI PET Diagnostic Performance: Whole-Body Disease Assessment and Comparison with 18F-FDG
3.2.6. 68Ga-FAPI PET Diagnostic Performance: False Positive and False Negative Findings
3.3. Theranostic Application
3.3.1. Clinical and Methodological Studies’ Characteristics
3.3.2. Pre- and Post-Treatment Imaging
3.3.3. FAPI Radioligand Therapy
4. Discussion
4.1. 68Ga-FAPI PET Diagnostic Studies: Clinical and Methodological Studies’ Characteristics
4.2. 68Ga-FAPI PET Diagnostic Performance: Primary BC Lesion
4.3. 68Ga-FAPI PET Diagnostic Performance: Whole-Body Disease Assessment
4.4. 68Ga-FAPI PET Diagnostic Performance: False Positive and False Negative Findings
4.5. FAPI Radioligand Therapy
5. Conclusions
6. Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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First Author | Year of Publication | Journal | Country | Study Design | Study Population | Indication for FAPI Imaging | Patients with BC (n) | PET Modality | FAPI Tracer | Activity | Scan Delay (p.i.) | FOV |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Loktev A [10] | 2018 | JNM | Germany | n.s. | Mixed tumors | Proof of concept | 1 | PET/CT | 68Ga-FAPI-02 | 222–312 MBq | 10 min, 1 h and 3 h | Vertex–upper thigh |
Giesel FL [8] | 2019 | JNM | Germany | R | Mixed tumors | Unmet diagnostic challenge or FAP-radioligand therapy suitability | 2 | PET/CT | 68Ga-FAPI-02, 68Ga-FAPI-04 | 122–336 MBq | 1 h and 3 h | Vertex–upper thigh |
Loktev A [12] | 2019 | JNM | Germany | R | Mixed tumors | Proof of concept | 2 | PET/CT | 68Ga-FAPI-04, 68Ga-FAPI-21, 68Ga-FAPI-46 | 210–267 MBq | 10 min, 1 h and 3 h | Vertex–upper thigh |
Kratochwil C [11] | 2019 | JNM | Germany | R | Mixed tumors | Unmet diagnostic challenge | 12 | PET/CT | 68Ga-FAPI-04 | 122–312 MBq | 1 h | Vertex– midthigh |
Meyer C [20] | 2020 | JNM | USA, Germany | R | Mixed tumors | Biodistribution and dosimetry | 1 | PET/CT | 68Ga-FAPI-46 | 214–246 MBq | 10 min, 1 and 3 h | Vertex– upper thigh |
Chen H [21] | 2020 | EJNMMI | China | P | Mixed tumors | Staging or restaging | 1 | PET/CT | 68Ga-FAPI-04 | 1.8–2.2 MBq/kg | 1 h | Head–upper thigh |
Pang Y [22] | 2020 | Clin Nucl Med | China | P | BC | Restaging | 1 | PET/CT | 68Ga-FAPI (n.o.s.) | n.s. | n.s. | Vertex–midthigh |
Shi X [23] | 2021 | EJNMMI | China | P | Mixed tumors | Hepatic nodules characterization | 1 | PET/CT | 68Ga-FAPI-04 | 96–260 MBq | 1 h | Vertex–upper thigh |
Chen H [24] | 2021 | EJNMMI | China | P | Mixed tumors | Inconclusive 18F-FDG findings | 4 | PET/CT | 68Ga-FAPI-04 | 1.8–2.2 MBq/kg | 1 h | Vertex–upper thigh |
Ballal S [25] | 2021 | EJNMMI | India, Germany, Chile | P | Mixed tumors | Biodistribution, pharmacokinetics and dosimetry | 20 | PET/CT | 68Ga-DOTA.SA.FAPi | 59.2–296 MBq | 1 h | Vertex–midthigh |
Zhao L [26] | 2021 | EJNMMI | China | R | Mixed tumors | Suspected peritoneal carcinomatosis | 1 | PET/CT | 68Ga-FAPI-04 | 1.8–2.2 MBq/kg | 1 h | Vertex–upper thigh |
Gündoğan C [27] | 2021 | Clin Nucl Med | Turkey | P | BC | Staging | 1 | PET/CT | 68Ga-FAPI-04 | n.s. | n.s. | Vertex–midthigh |
Can C [28] | 2021 | Clin Nucl Med | Turkey | P | BC | Staging | 1 | PET/CT | 68Ga-FAPI-04 | n.s. | n.s. | Vertex–upper thigh |
Kömek H [29] | 2021 | Ann Nucl Med | Turkey | P | BC | Staging or restaging | 20 | PET/CT | 68Ga-FAPI-04 | 2 MBq/kg | 1 h | Vertex–midthigh |
Dendl K [6] | 2021 | EJNMMI | Germany, South Africa | R | Mixed tumors | Unmet diagnostic challenge or FAP-radioligand therapy suitability | 14 | PET/CT | 68Ga-FAPI-02, 68Ga-FAPI-04, 68Ga-FAPI-46, 68Ga-FAPI-74 | 52–325 MBq | 1 h | Vertex–midthigh |
Zheng S [30] | 2021 | EJNMMI | China | P | BC | Staging | 1 | PET/CT | 68Ga-FAPI (n.o.s.) | n.s. | n.s. | Head–upper thigh |
Zheng S [31] | 2021 | Ann Nucl Med | China | R | Mixed tumors | Staging or restaging | 16 | PET/CT | 68Ga-FAPI-04 | 3.7 MBq/kg | 30–60 min | Head–upper thigh |
Elboga U [32] | 2021 | Ann Nucl Med | Turkey | R | BC | Staging or restaging | 48 | PET/CT | 68Ga-FAPI-04 | 2 MBq/kg | 1 h | Vertex–midthigh |
Wu J [33] | 2021 | Front Oncol | China | R | Mixed tumors | Bone metastases detection | 1 | PET/CT | 68Ga-FAPI-04 | 1.85–2.59 MBq/kg | 65 ± 5 min | Skull base–midthigh |
Kömek H [34] | 2021 | Mol Imaging Radionucl Ther | Turkey | n.s. | BC | Staging | 1 | PET/CT | 68Ga-FAPI-04 | n.s. | n.s. | Vertex–midthigh |
Çermik TF [35] | 2022 | Clin Nucl Med | Turkey | P | Mixed tumors | Staging, restaging, treatment response evaluation | 1 | PET/CT | 68Ga-FAPI-04 | 1.85 MBq/kg | 1 h | Vertex–upper thigh |
Xu T [36] | 2022 | Clin Nucl Med | China | P | BC | Staging | 1 | PET/CT | 68Ga-FAPI-04 | n.s. | n.s. | Vertex–midthigh |
Shang Q [37] | 2022 | EJNMMI | China | P | BC | Staging | 1 | PET/CT | 68Ga-FAPI-04 | n.s. | n.s. | Head–upper thigh |
Mona CE [2] | 2022 | JNM | USA | P | Mixed tumors | Biodistribution, immuno-histochemistry correlation | 2 | PET/CT | 68Ga-FAPI-46 | 184 ± 3 MBq | 63 ± 10 min | Vertex–midthigh |
Wang Q [38] | 2022 | Clin Nucl Med | China | P | BC | Staging | 1 | PET/CT | 68Ga-FAPI-04 | n.s. | n.s. | Vertex–midthigh |
Backhaus P [39] | 2022 | Radiology | Germany | R | BC | Staging, restaging after treatment | 19 | PET/CT, PET/MR | 68Ga-FAPI-46 | 149 ± 48 MBq | 79 min | n.s. |
Gungor S [40] | 2022 | Clin Nucl Med | Turkey | P | BC | Restaging | 1 | PET/CT | 68Ga-FAPI (n.o.s.) | n.s | n.s. | Vertex–midthigh |
First Author | Patients (n) | Age (Years) | 68Ga-FAPI Activity | 18F-FDG Activity | Time between 68Ga-FAPI and 18F-FDG Scans | PET Image Analysis | 68Ga-FAPI >18F-FDG | 68Ga-FAPI ≤ 18F-FDG |
---|---|---|---|---|---|---|---|---|
Kömek H [29] | 20 | 32–65 | 2 MBq/kg | 3.5–5.5 MBq/kg | 1 week | Semiquantitative (68Ga-FAPI and 18F-FDG) | - Higher sensitivity in detecting primary BC (100% vs. 78.2% 18F-FDG) | - Similar specificity in detecting primary BC (100% 18F-FDG vs. 95.6% 68Ga-FAPI) - Not a statistically significant difference between the two tracers in SUVmax values of hepatic metastases (p > 0.05) |
- Significantly higher SUVmax values in primary BC, lymph nodes, lung and bone metastases (p < 0.05) | ||||||||
- Significantly higher TBR values in BC, hepatic, bone, brain and lung metastases (p < 0.05). | ||||||||
- Lower background activity and higher uptake in subcentimetric lesions | ||||||||
- Lower physiological uptake in liver, bone and brain | ||||||||
Elboga U [32] | 48 | 53.3 ± 11.7 | 2 MBq/kg | 3.5–5.5 MBq/kg | Max 1 week | Semiquantitative (68Ga-FAPI and 18F-FDG) | - More lesions detected in breast, lymph nodes and bone | - |
- Higher SUVmax values in primary BC, lymph nodes, lung, liver and bone metastases | ||||||||
- Higher SUVmax values for ILC, but not statistically significant (due to the low number of ILC patients) | ||||||||
- Change in therapeutic approach of 12 pts defined as PD by 68Ga-FAPI imaging (reported as PMR, CMR or SD by 18F-FDG) | ||||||||
- Better assessment of lesions in the first month of post-chemotherapy period | ||||||||
Ballal S [25] | 20 | 30–66 | 59.2–296 MBq | 185–370 MBq | 1 week | Qualitative and semiquantitative (68Ga-FAPI and 18F-FDG) | - A remarkably higher SULpeak and SULavg brain metastases-to-normal brain ratio (due to lower brain parenchyma physiological uptake) - Outstandingly higher uptake values for Krukenberg metastases (p < 0.0001) | - Comparable results for detection of primary BC, with comparable SUL values between the two tracers - Similar diagnostic accuracy for both tracers |
Dendl K [6] | 14 | 59.5 (median) | 52–325 MBq | 251–300 MBq | 12.5 days (median) | Semiquantitative (68Ga-FAPI and 18F-FDG) | - High uptake, resulting in sharp contrasts in primary and metastatic lesions | - Higher 18F-FDG uptake in lung metastases (13.7 vs. 6.6; p = 0.18) |
- Slight advantages of mean SUVmax in all metastatic lesions (8.2 vs. 7.8; p = 0.131) | ||||||||
- Favorable mean SUVmax in lymph nodes (7.1 vs. 6.3; p = 0.753), bone (10.1 vs. 7.4; p = 0.138) and liver metastases (5.9 vs. 5.1; p = 0.593) | ||||||||
- TBRs slightly advantageous in regional lymph nodes (31.9 vs. 27.4; p = 0.6) and, significantly, in distant metastases (13.0 vs. 5.7; p = 0.047) |
First Author | Year of Publication | Journal | Country | Study Design | Patients with BC (n) | BC Clinical Setting | Previous Treatments | Therapeutic FAPI Tracer | Overall Activity (GBq) | Treatment Response | Adverse Events |
---|---|---|---|---|---|---|---|---|---|---|---|
Assadi M [41] | 2021 | CNM | Iran | P | 5 | Metastatic progressive disease | SUR + CHT + EBRT | 177Lu-FAPI-46 | 1.85–12.95 (range) | 3/5 SD 2/5 PD 3/5 ECOGPS stable 2/5 ECOGPS worsening PFS not evaluated OS >2.0–5.0 months | Worsening of pain (1/5 pts) |
Ballal S [25] | 2021 | EJNMMI | India | R | 1 | Metastatic progressive disease | n.s. | 177Lu-DOTA.SA.FAPi | 3.2 | Reduction of pain PFS and OS not evaluated | No AEs |
Ballal S [42] | 2021 | Pharmaceuticals | India | P | 4 | Metastatic progressive disease | n.s. | 177Lu-DOTA.SA.FAPI (3 pts) 177Lu-DOTAGA.(SA.FAPI) (1 pt) | 2.96 n.s. | Clinical response in all pts (symptoms) PFS and OS not evaluated | No AEs |
Baum RP [43] | 2022 | JNM | Germany, USA, Singapore | R | 4 | Metastatic progressive disease | EBRT, chemo-embolization, 177Lu-HER2-ligand,177Lu-diphosphonate, CHT, hormonal therapy | 177Lu-FAP-2286 | 8.3–14-4 (range) | PD after 2 cycles PFS not evaluated 3 pts alive after 18 months from 1 FAPI-RLT cycle | Pain, anemia, leukocytopenia (G1, G2, G3) |
Lindner T [9] | 2018 | JNM | Germany | P | 1 | Metastatic progressive disease | n.s. | 90Y-FAPI-04 | 2.9 | Reduction of pain PFS and OS not evaluated | n.s. |
Ratke H [44] | 2021 | CNM | Germany | P | 1 | Metastatic progressive disease | Hormonal therapy, CHT, diphosphonates | 90Y-FAPI-46 | 28.1 | SD PFS not evaluated OS 11 months | n.s. |
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Taralli, S.; Lorusso, M.; Perrone, E.; Perotti, G.; Zagaria, L.; Calcagni, M.L. PET/CT with Fibroblast Activation Protein Inhibitors in Breast Cancer: Diagnostic and Theranostic Application—A Literature Review. Cancers 2023, 15, 908. https://doi.org/10.3390/cancers15030908
Taralli S, Lorusso M, Perrone E, Perotti G, Zagaria L, Calcagni ML. PET/CT with Fibroblast Activation Protein Inhibitors in Breast Cancer: Diagnostic and Theranostic Application—A Literature Review. Cancers. 2023; 15(3):908. https://doi.org/10.3390/cancers15030908
Chicago/Turabian StyleTaralli, Silvia, Margherita Lorusso, Elisabetta Perrone, Germano Perotti, Luca Zagaria, and Maria Lucia Calcagni. 2023. "PET/CT with Fibroblast Activation Protein Inhibitors in Breast Cancer: Diagnostic and Theranostic Application—A Literature Review" Cancers 15, no. 3: 908. https://doi.org/10.3390/cancers15030908
APA StyleTaralli, S., Lorusso, M., Perrone, E., Perotti, G., Zagaria, L., & Calcagni, M. L. (2023). PET/CT with Fibroblast Activation Protein Inhibitors in Breast Cancer: Diagnostic and Theranostic Application—A Literature Review. Cancers, 15(3), 908. https://doi.org/10.3390/cancers15030908