Design and validation of fibroblast activation protein alpha targeted imaging and therapeutic agents

Roy, Jyoti; Hettiarachchi, Suraj U.; Kaake, Miranda; Mukkamala, Ramesh

doi:10.7150/thno.41409

Cited by 42 publications

(43 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whilst not statistically significant in a mixed cohort, sub-group analysis of only squamous carcinoma cases was statistically significant, in contrast to findings of Chen et al 74 In what is emerging as a common theme, these two studies used different antibodies, grading systems and scored either whole slides or tissue micro-arrays; this may account for the discordant results in these studies. Such discrepancies are concerning though as FAP is currently regarded as a CAF target for molecular-based imaging 75 and therapeutic targeting 76 . Without a clear understanding of its role in CAF biology, such trials might produce inconsistent results.…”

Section: Cellular Procceses In Cafsmentioning

confidence: 99%

Characterising cancer-associated fibroblast heterogeneity in non-small cell lung cancer: a systematic review and meta-analysis

Irvine

Waise

Green

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with evidence suggesting they represent a heterogeneous population. This study summarises the prognostic role of all proteins characterised in CAFs with immunohistochemistry in non-small cell lung cancer thus far. The functions of these proteins in cellular processes crucial to CAFs are also analysed. Five databases were searched to extract survival outcomes from published studies and statistical techniques, including a novel method, used to capture missing values from the literature. A total of 26 proteins were identified, 21 of which were combined into 7 common cellular processes key to CAFs. Quality assessments for sensitivity analyses were carried out for each study using the REMARK criteria whilst publication bias was assessed using funnel plots. Random effects models consistently identified the expression of podoplanin (Overall Survival (OS)/Disease-specific Survival (DSS), univariate analysis HR 2.25, 95% CIs 1.80–2.82) and α-SMA (OS/DSS, univariate analysis HR 2.11, 95% CIs 1.18–3.77) in CAFs as highly prognostic regardless of outcome measure or analysis method. Moreover, proteins involved in maintaining and generating the CAF phenotype (α-SMA, TGF-β and p-Smad2) proved highly significant after sensitivity analysis (HR 2.74, 95% CIs 1.74–4.33) supporting attempts at targeting this pathway for therapeutic benefit.

show abstract

Section: Cellular Procceses In Cafsmentioning

confidence: 99%

Characterising cancer-associated fibroblast heterogeneity in non-small cell lung cancer: a systematic review and meta-analysis

Irvine

Waise

Green

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The SPECT analysis visualized tracer accumulation in the solid tumors. A co-injection of cold FL excess blocked the tumor uptake which proofed the FAP-mediated binding and retention of the radiotracer [ 38 ].…”

Section: Targeting Of the Tumor Microenvironmentmentioning

confidence: 99%

Development of Radiotracers for Breast Cancer—The Tumor Microenvironment as an Emerging Target

Heesch

Maurer

Stickeler

et al. 2020

Cells

View full text Add to dashboard Cite

Molecular imaging plays an increasingly important role in the diagnosis and treatment of different malignancies. Radiolabeled probes enable the visualization of the primary tumor as well as the metastases and have been also employed in targeted therapy and theranostic approaches. With breast cancer being the most common malignancy in women worldwide it is of special interest to develop novel targeted treatments. However, tumor microenvironment and escape mechanisms often limit their therapeutic potential. Addressing tumor stroma associated targets provides a promising option to inhibit tumor growth and angiogenesis and to disrupt tumor tissue architecture. This review describes recent developments on radiolabeled probes used in diagnosis and treatment of breast cancer especially in triple negative type with the focus on potential targets offered by the tumor microenvironment, like tumor associated macrophages, cancer associated fibroblasts, and endothelial cells.

show abstract

“…Another 99m Tc-labeled FAP-targeting ligand (FL-L3) was lately reported by Roy et al, which includes the radiometal 99m Tc coordinated via the 99m Tc(V)-oxo moiety while 8-amino-octanoic acid served as the linker between the metal chelator and the FAP inhibitor [ 115 ]. [ 99m Tc]Tc-FL-L3 demonstrated high affinity and specificity for FAP when the FAP-transfected human embryonic kidney HEK 293 cell line was used.…”

Section: Development Of Radiolabeled-based Fap Tracers For Tumor Stroma Mediated Nuclear Imaging and Radionuclide-based Therapymentioning

confidence: 99%

New Frontiers in Cancer Imaging and Therapy Based on Radiolabeled Fibroblast Activation Protein Inhibitors: A Rational Review and Current Progress

et al. 2021

View full text Add to dashboard Cite

Over the past decade, the tumor microenvironment (TME) has become a new paradigm of cancer diagnosis and therapy due to its unique biological features, mainly the interconnection between cancer and stromal cells. Within the TME, cancer-associated fibroblasts (CAFs) demonstrate as one of the most critical stromal cells that regulate tumor cell growth, progression, immunosuppression, and metastasis. CAFs are identified by various biomarkers that are expressed on their surfaces, such as fibroblast activation protein (FAP), which could be utilized as a useful target for diagnostic imaging and treatment. One of the advantages of targeting FAP-expressing CAFs is the absence of FAP expression in quiescent fibroblasts, leading to a controlled targetability of diagnostic and therapeutic compounds to the malignant tumor stromal area using radiolabeled FAP-based ligands. FAP-based radiopharmaceuticals have been investigated strenuously for the visualization of malignancies and delivery of theranostic radiopharmaceuticals to the TME. This review provides an overview of the state of the art in TME compositions, particularly CAFs and FAP, and their roles in cancer biology. Moreover, relevant reports on radiolabeled FAP inhibitors until the year 2021 are highlighted—as well as the current limitations, challenges, and requirements for those radiolabeled FAP inhibitors in clinical translation.

show abstract

Design and validation of fibroblast activation protein alpha targeted imaging and therapeutic agents

Cited by 42 publications

References 48 publications

Characterising cancer-associated fibroblast heterogeneity in non-small cell lung cancer: a systematic review and meta-analysis

Characterising cancer-associated fibroblast heterogeneity in non-small cell lung cancer: a systematic review and meta-analysis

Development of Radiotracers for Breast Cancer—The Tumor Microenvironment as an Emerging Target

New Frontiers in Cancer Imaging and Therapy Based on Radiolabeled Fibroblast Activation Protein Inhibitors: A Rational Review and Current Progress

Contact Info

Product

Resources

About