Fibroblast Activation Protein (FAP) specific PET for advanced target volume delineation in glioblastoma

Windisch, Paul; Röhrich, Manuel; Regnery, Sebastian; Tonndorf-Martini, Eric; Held, T.; Lang, Kristin; Bernhardt, Denise; Rieken, Stefan; Giesel, Frederik L.; Haberkorn, Uwe; Debus, Jürgen; Adeberg, Sebastian

doi:10.1016/j.radonc.2020.06.040

Cited by 52 publications

(45 citation statements)

References 22 publications

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“…Another limitation is that the total number of patients who received FAP-specific PET for a given indication cannot be determined exactly. While some publications report that they analyze the same patient collective as another publication [23,35], it cannot be helped that some publications from the same group contain at least a subset of patients that is analyzed more than once.…”

Section: Discussionmentioning

confidence: 99%

“…It observed that applying a 7-fold threshold of intensity compared to healthy-appearing normal brain tissue resulted in PET-based gross tumor volumes (PET-GTVs) equal to those based on MRI (MRI-GTVs). MRI-and PET-GTVs were incongruent, and adding PET-to MRI-GTVs resulted in an increase of the MRI-GTV by on average 45.9% [23].…”

Section: Brainmentioning

confidence: 99%

“…Three studies describe results of FAP-specific PET performed on the same group of glioma patients [23,34,35]. The first analysis by Röhrich et al included 13 glioblastomas (GBMs), one grade III and three grade II gliomas.…”

Section: Brainmentioning

confidence: 99%

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Clinical Results of Fibroblast Activation Protein (FAP) Specific PET and Implications for Radiotherapy Planning: Systematic Review

Windisch

Zwahlen

Koerber

et al. 2020

Cancers

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Small molecules targeting fibroblast activation protein (FAP) have emerged as a new group of tracers for positron emission tomography (PET) in 2018. The purpose of this systematic review is therefore to summarize the evidence that has been gathered to date in patients and to discuss its possible implications for radiotherapy planning. The MEDLINE database was searched for the use of FAP-specific PET in cancer patients and the records were screened according to PRISMA guidelines. Nineteen studies were included. While dedicated analyses of FAP-specific PET for radiotherapy planning were available for glioblastoma, head and neck cancers, lung cancer, and tumors of the lower gastrointestinal tract, there is still very limited data for several epidemiologically significant cancers. In conclusion, FAP-specific PET represents a promising imaging modality for radiotherapy planning that warrants further research.

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Section: Discussionmentioning

confidence: 99%

Section: Brainmentioning

confidence: 99%

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Clinical Results of Fibroblast Activation Protein (FAP) Specific PET and Implications for Radiotherapy Planning: Systematic Review

Windisch

Zwahlen

Koerber

et al. 2020

Cancers

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“…1). Among these, the 68 Ga-labeled ligands have been extensively studied and 68 Ga-FAPI-04 has applied in clinical imaging for various types of cancers that have a high tumor-tonoise ratio [7,8,10,[12][13][14][15][16]. However, the 68 Ga-labeled tracers were limited in the availability of radionuclide from 68 Ge/ 68 Ga-generators and have a relatively short half-life 68 Ga (T 1/2 = 67.7 min, 88.9 % β + ).…”

Section: Introductionmentioning

confidence: 99%

Preclinical Evaluation and Pilot Clinical Study of 18F-AlF-labeled FAPI-Tracers for PET Imaging of Cancer Associated Fibroblasts

Li²,

Wang

et al. 2021

Preprint

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Background The recent development of many different types of radiotracers that target the fibroblast activation protein (FAP) has been promising for tumor diagnosis. Here, we set out to develop 18F-labeled FAP tracers for cancer-associated fibroblast imaging and evaluated the potential of these tracers for clinical application. Methods The non-radioactive reference compounds and labeling precursors were synthesized using organic chemistry and the binding affinities were identified using surface plasmon resonance. Both radioligands (18F-P-FAPI and 18F-FAPI-42) were produced in an automated manner via complexation of Al18F. For in vitro characterization of 18F-P-FAPI and 18F-FAPI-42, we conducted studies to determine the partition coefficients, stability, cellular uptake, internalization, and efflux. In vivo biodistribution studies and microPET imaging of 18F-P-FAPI and 18F-FAPI-42, in comparison to 68Ga-FAPI-04, were conducted on the A549-FAP tumor bearing mice. Finally, one nasopharyngeal cancer patient underwent whole-body PET/CT after being injected with 18F-P-FAPI. Results Both 18F-P-FAPI and 18F-FAPI-42 were successful prepared with high specificity, rapid internalization, and potent affinity binding toward FAP. Compared to 18F-FAPI-42, 18F-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo. Furthermore, in vivo studies of 18F-P-FAPI in the A549-FAP tumor model indicated a higher tumor uptake than 18F-FAPI-42 and 68Ga-FAPI-04. An initial diagnostic application in patient with nasopharyngeal cancer, 18F-P-FAPI and 18F-FDG PET/CT showed comparable results for both primary tumors and lymph node metastases. Conclusion The radiofluorinated FAP-ligands demonstrated promising characteristics in their preclinical evaluation, and the feasibility of cancer-associated fibroblasts imaging was demonstrated using PET studies.

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“…AB Hesterberg et al imaging strategies [41][42][43][44][45][46]. Similar to FAP, Thy-1 cell surface antigen (THY1) is also overexpressed in prostate CAFs [47], and it may have a role in regulating cancer stem cells [48].…”

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confidence: 99%

A distinct repertoire of cancer‐associated fibroblasts is enriched in cribriform prostate cancer

Hesterberg

Rios

Wolf

et al. 2021

The Journal of Pathology CR

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Outcomes for men with localized prostate cancer vary widely, with some men effectively managed without treatment on active surveillance, while other men rapidly progress to metastatic disease despite curative-intent therapies. One of the strongest prognostic indicators of outcome is grade groups based on the Gleason grading system. Gleason grade 4 prostate cancer with cribriform morphology is associated with adverse outcomes and can be utilized clinically to improve risk stratification. The underpinnings of disease aggressiveness associated with cribriform architecture are not fully understood. Most studies have focused on genetic and molecular alterations in cribriform tumor cells; however, less is known about the tumor microenvironment in cribriform prostate cancer. Cancer-associated fibroblasts (CAFs) are a heterogeneous population of fibroblasts in the tumor microenvironment that impact cancer aggressiveness. The overall goal of this study was to determine if cribriform prostate cancers are associated with a unique repertoire of CAFs. Radical prostatectomy whole-tissue sections were analyzed for the expression of fibroblast markers (ASPN in combination with FAP, THY1, ENG, NT5E, TNC, and PDGFRβ) in stroma adjacent to benign glands and in Gleason grade 3, Gleason grade 4 cribriform, and Gleason grade 4 noncribriform prostate cancer by RNAscope ® . Halo ® Software was used to quantify percent positive stromal cells and expression per positive cell. The fibroblast subtypes enriched in prostate cancer were highly heterogeneous. Both overlapping and distinct populations of low abundant fibroblast subtypes in benign prostate stroma were enriched in Gleason grade 4 prostate cancer with cribriform morphology compared to Gleason grade 4 prostate cancer with noncribriform morphology and Gleason grade 3 prostate cancer. In addition, gene expression was distinctly altered in CAF subtypes adjacent to cribriform prostate cancer. Overall, these studies suggest that cribriform prostate cancer has a unique tumor microenvironment that may distinguish it from other Gleason grade 4 morphologies and lower Gleason grades.

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Fibroblast Activation Protein (FAP) specific PET for advanced target volume delineation in glioblastoma

Cited by 52 publications

References 22 publications

Clinical Results of Fibroblast Activation Protein (FAP) Specific PET and Implications for Radiotherapy Planning: Systematic Review

Clinical Results of Fibroblast Activation Protein (FAP) Specific PET and Implications for Radiotherapy Planning: Systematic Review

Preclinical Evaluation and Pilot Clinical Study of 18F-AlF-labeled FAPI-Tracers for PET Imaging of Cancer Associated Fibroblasts

A distinct repertoire of cancer‐associated fibroblasts is enriched in cribriform prostate cancer

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Fibroblast Activation Protein (FAP) specific PET for advanced target volume delineation in glioblastoma

Cited by 52 publications

References 22 publications

Clinical Results of Fibroblast Activation Protein (FAP) Specific PET and Implications for Radiotherapy Planning: Systematic Review

Clinical Results of Fibroblast Activation Protein (FAP) Specific PET and Implications for Radiotherapy Planning: Systematic Review

Preclinical Evaluation and Pilot Clinical Study of 18F-AlF-labeled FAPI-Tracers for PET&nbsp;Imaging of Cancer Associated Fibroblasts

A distinct repertoire of cancer‐associated fibroblasts is enriched in cribriform prostate cancer

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Preclinical Evaluation and Pilot Clinical Study of 18F-AlF-labeled FAPI-Tracers for PET Imaging of Cancer Associated Fibroblasts