Correlation of <sup>68</sup>Ga-FAPi-46 PET Biodistribution with FAP Expression by Immunohistochemistry in Patients with Solid Cancers: Interim Analysis of a Prospective Translational Exploratory Study

Mona, Christine E.; Benz, Matthias; Hikmat, Firas; Grogan, Tristan; Lückerath, Katharina; Razmaria, Aria; Riahi, Rana; Slavik, Roger; Girgis, Mark D.; Carlucci, Giuseppe; Kelly, Kimberly A.; French, Samuel W.; Czernin, Johannes; Dawson, David W.; Calais, Jérémie

doi:10.2967/jnumed.121.262426

Cited by 89 publications

(82 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FAP expression in healthy tissues is negligible. ( 12,13,16,17 ) We have recently reported the discovery of OncoFAP, the small molecule FAP-targeting agent with the highest affinity reported so far. ( 18 ) Proof-of-concept targeting studies with [ 68 Ga]Ga-OncoFAP-DOTAGA ( 68 Ga-OncoFAP), a PET tracer based on OncoFAP, have confirmed excellent biodistribution in patients with different primary and metastatic solid malignancies.…”

Section: Introductionmentioning

confidence: 99%

A novel dimeric FAP-targeting small molecule-radio conjugate with high and prolonged tumour uptake

Galbiati

Zana

Bocci

et al. 2022

Preprint

View full text Add to dashboard Cite

Imaging procedures based on small molecule-radio conjugates (SMRCs) targeting fibroblast activation protein (FAP) have recently emerged as a powerful tool for the diagnosis of a wide variety of tumours. However, the therapeutic potential of radiolabeled FAP-targeting agents is limited by their short residence time in neoplastic lesions. In this work, we present the development and in vivo characterization of BiOncoFAP, a new dimeric FAP-binding motif with extended tumour residence time and favorable tumour-to-organ ratio. Methods: The binding properties of BiOncoFAP and its monovalent OncoFAP analogue were assayed against recombinant hFAP. Preclinical experiments with [177Lu]Lu-OncoFAP-DOTAGA (177Lu-OncoFAP) and [177Lu]Lu-BiOncoFAP-DOTAGA (177Lu-BiOncoFAP) were performed in mice bearing FAP-positive HT-1080 tumours. OncoFAP and BiOncoFAP displayed comparable sub-nanomolar dissociation constants towards hFAP in solution, but the bivalent BiOncoFAP bound more avidly to the target immobilized on solid supports. In a comparative biodistribution study, 177Lu-BiOncoFAP exhibited a more stable and prolonged tumour uptake than 177Lu-OncoFAP (~20% ID/g vs ~4% ID/g, at 24h p.i., respectively). Notably, 177Lu-BiOncoFAP showed favorable tumour-to-organ ratios with low kidney uptake. Both 177Lu-OncoFAP and 177Lu-BiOncoFAP displayed potent anti-tumour efficacy when administered at therapeutic doses in tumour bearing mice. 177Lu-BiOncoFAP is a promising candidate for radioligand therapy of cancer, with favorable in vivo tumour-to-organ ratio, long tumour residence time and potent anti-cancer efficacy.

show abstract

Section: Introductionmentioning

confidence: 99%

A novel dimeric FAP-targeting small molecule-radio conjugate with high and prolonged tumour uptake

Galbiati

Zana

Bocci

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The origin, number, and distribution of FAP-expressing CAFs as well as the number of FAP molecules per cell may differ among tumors. Mona et al [20] reported the presence of a strong association between tumor 68 Ga-FAPI uptake intensity and histopathological FAP expression in colon cancer. We expected variations in intratumoral tracer distribution in treatment-naïve patients with speci c histopathologic types of CRC.…”

Section: Discussionmentioning

confidence: 99%

68Ga-FAPI improves tumor staging in patients with colorectal cancer: comparing to 18F-FDG PET/CT

Lin

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

Purpose Gallium-68 (68Ga)-labeled fibroblast-activation protein inhibitor (FAPI) is a novel tracer that binds fibroblast-activation protein (FAP), which is overexpressed in colorectal cancers with a prominent stroma including cancer-associated fibroblasts (CAFs). The present study aimed to compare the diagnostic performance of 68Ga-FAPI positron emission tomography (PET)/computed tomography (CT) with that of fluorine-18 (18F)-fluorodeoxyglucose (FDG) PET/CT in primary and metastatic colorectal cancer lesions. Methods This prospective study included the image analyses of 37 patients with colorectal cancer who were sequentially evaluated using PET/CT with 18F-FDG and 68Ga-FAPI. Tracer uptakes were compared using Wilcoxon’s signed-rank test. Results The cohort comprised 37 patients, including 18 treatment-naïve patients and 19 post-treatment patients. In primary colorectal cancer lesions, the average 68Ga-FAPI and 18F-FDG maximum standardized uptake values (SUVmax) were 12.5 ± 4.8 and 13.2 ± 5.7 (P = 0.38), respectively, in the treatment-naïve group and 6.0 ± 4.3 and 7.9 ± 7.2, respectively, in the neoadjuvant chemotherapy group (P = 0.09); the detection rate was 100% with both tracers (18/18). The SUVmax value of 68Ga-FAPI in signet-ring/mucinous carcinomas (12.3 ± 5.2) was higher than that of 18F-FDG (8.3 ± 4.0) (P = 0.03). In addition, the average 68Ga-FAPI uptake was lower than that of 18F-FDG in poorly differentiated carcinomas (12.7 ± 3.7 vs. 18.1 ± 4.1, P = 0.04). Compared with 18F-FDG PET/CT, clinical TNM staging based on 68Ga-FAPI PET/CT led to upstaging in 6 patients (16.2%) and downstaging in 3 patients (8.1%). In peritoneal and liver metastases, both the SUVmax and the target/background ratio were higher with 68Ga-FAPI compared to 18F-FDG (3.7 vs. 2.6, P = 0.02, and 6.5 vs. 0.89, P = 0.01, respectively). Conclusion As a novel PET/CT tracer, 68Ga-FAPI showed its advantage in the detection of lymph nodes, and distant metastases, which improved staging of CRC.

show abstract

“…This case suggests that the expression of FAP in hormone-sensitive organs such as the breast and uterus may undergo a physiological increase after pregnancy and during lactation (133). The latest study by Christine E. Mona et al showed that the highest 68 Ga-FAPI-46 PET signal in the normal organ was the bladder due to the urinary bladder due to urinary excretion and the uterus due to normal myometrial FAP expression (134).…”

Section: Uterusmentioning

confidence: 98%

“…The latest study by Christine E. Mona et al. showed that the highest 68 Ga-FAPI-46 PET signal in the normal organ was the bladder due to the urinary bladder due to urinary excretion and the uterus due to normal myometrial FAP expression ( 134 ).…”

Section: Pelvic Organsmentioning

confidence: 99%

FAPI PET/CT in the Diagnosis of Abdominal and Pelvic Tumors

Yang

Hou

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) is currently a standard imaging examination used in clinical practice, and plays an essential role in preoperative systemic evaluation and tumor staging in patients with tumors. However, 18F-FDG PET/CT has certain limitations in imaging of some tumors, like gastric mucus adenocarcinoma, highly differentiated hepatocellular carcinoma, renal cell carcinoma, and peritoneal metastasis. Therefore, to search for new tumor diagnosis methods has always been an important topic in radiographic imaging research. Fibroblast activation protein (FAP) is highly expressed in many epithelial carcinomas, and various isotope-labelled fibroblast activation protein inhibitors (FAPI) show lower uptake in the brain and abdominal tissues than in tumor, thus achieving high image contrast and good tumor delineation. In addition to primary tumors, FAPI PET/CT is better than FDG PET/CT for detecting lymph nodes and metastases. Additionally, the highly selective tumor uptake of FAPI may open up new application areas for the non-invasive characterization, staging of tumors, as well as monitoring tumor treatment efficacy. This review focuses on the recent research progress of FAPI PET/CT in the application to abdominal and pelvic tumors, with the aim of providing new insights for diagnostic strategies for tumor patients, especially those with metastases.

show abstract

Correlation of ⁶⁸Ga-FAPi-46 PET Biodistribution with FAP Expression by Immunohistochemistry in Patients with Solid Cancers: Interim Analysis of a Prospective Translational Exploratory Study

Abstract: Visual Abstract

Cited by 89 publications

References 20 publications

A novel dimeric FAP-targeting small molecule-radio conjugate with high and prolonged tumour uptake

A novel dimeric FAP-targeting small molecule-radio conjugate with high and prolonged tumour uptake

68Ga-FAPI improves tumor staging in patients with colorectal cancer: comparing to 18F-FDG PET/CT

FAPI PET/CT in the Diagnosis of Abdominal and Pelvic Tumors

Contact Info

Product

Resources

About

Correlation of 68Ga-FAPi-46 PET Biodistribution with FAP Expression by Immunohistochemistry in Patients with Solid Cancers: Interim Analysis of a Prospective Translational Exploratory Study

Abstract: Visual Abstract

Cited by 89 publications

References 20 publications

A novel dimeric FAP-targeting small molecule-radio conjugate with high and prolonged tumour uptake

A novel dimeric FAP-targeting small molecule-radio conjugate with high and prolonged tumour uptake

68Ga-FAPI improves tumor staging in patients with colorectal cancer: comparing to 18F-FDG PET/CT

FAPI PET/CT in the Diagnosis of Abdominal and Pelvic Tumors

Contact Info

Product

Resources

About

Correlation of ⁶⁸Ga-FAPi-46 PET Biodistribution with FAP Expression by Immunohistochemistry in Patients with Solid Cancers: Interim Analysis of a Prospective Translational Exploratory Study