Search

Purpose: Due to limited imaging options, the visualization of a local relapse of prostate cancer used to pose a considerable challenge. However, since the integration of 18F-PSMA-1007-PET/CT into the clinic, a relapsed tumor can now easily be detected by hybrid imaging. The present study aimed to evaluate and map the allocate relapse in a large cohort of prostate cancer patients focusing on individual patient management conclusions for radiation therapy. Procedures: The current study included 135 men with prostate cancer after primary treatment who underwent 18F-PSMA-1007-PET/CT due to biochemical relapse detecting a local relapse. Imaging data were reassessed and analyzed with regard to relapse locations. For the correlation of tumor foci with clinical data, we used binary logistic regression models as well as the Kruskal–Wallis test and Mann–Whitney test. Results: In total, 69.6% of all patients (mean age: 65 years) underwent prostatectomy while 30.4% underwent radiation therapy. PET imaging detected most frequently a unifocal relapse (72.6%). There was a statistically significantly higher rate of ipsilateral cases among the relapsed tumors. Comparing both treatment approaches, tumors relapsed most commonly within the posterior region after surgery and transition/peripheral zone after radiation therapy, respectively. Conclusions: The present study confirms that 18F-PSMA-1007-PET/CT is highly suitable for the localization and allocation of a local relapse in patients with prostate cancer. The data enable further optimizing dose prescriptions and target volume delineations of radiation therapy in the future. [ABSTRACT FROM AUTHOR]

Aim/Purpose: Fibroblast activation protein (FAP) is overexpressed by cancer-associated fibroblasts. However, activated fibroblasts have been shown to play a significant role also in certain benign conditions such as wound healing or chronic inflammation. Therefore, the current study aimed to identify whether FAPI uptake might differ between malignant lesions and benign conditions. Material and Methods: We retrospectively analyzed 155 patients with various cancer types who received [68 Ga]-FAPI-04/02-PET/CT between July 2017 and March 2020. SUVmax, SUVmean, and lesion-to-background ratios (LBR) of FAPI uptake were measured in benign processes compared to malignant lesions (primary and/or 2 exemplary metastases). In addition, receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive capabilities of semiquantitative PET/CT parameters. Furthermore, the sensitivity, specificity, optimal cutoff value, and 95% confidence interval (CI) were determined for each parameter. Results: Benign lesions exhibited significantly lower FAPI uptake compared to malignant lesions (mean SUVmax benign vs. malignant: 4.2 vs. 10.6; p < 0.001). In ROC analysis, cutoff values of these lesions (benign vs. malignant) were established based on SUVmax, SUVmean, and LBR. The SUVmax cutoff value for all lesions was 5.5 and the corresponding sensitivity, specificity, accuracy, and AUC were 78.8%, 85.1%, 82.0%, and 0.89%, respectively. Conclusion: Our aim was to systematically analyze the pattern of FAPI uptake in benign and malignant processes. This investigation demonstrates that FAPI uptake might be useful to differentiate malignant and benign findings due to different patho-physiological origins. [ABSTRACT FROM AUTHOR]

Aim/Purpose: Fibroblast activation protein-(FAP)-ligands, a novel class of tracers for PET/CT imaging, demonstrated promising results in previous studies in various malignancies compared to standard [18F]FDG PET/CT. 68Ga-labeled fibroblast activation protein inhibitor-([68Ga]Ga-DOTA-FAPI)-PET/CT impresses with sharp contrasts in terms of high tumor uptake and low background noise leading to clear delineation. [18F]FDG PET/CT has limited accuracy in bladder cancer due to high background signal. Therefore, we sought to evaluate the diagnostic potential of [68Ga]FAPI in patients with bladder cancer. Material and Methods: This retrospective analysis consisted of 8 patients (median age 66), 7 of whom underwent both [68Ga]FAPI and [18F]FDG PET/CT scans with a median time interval of 5 days (range 1–20 days). Quantification of tracer uptake was determined with SUVmax and SUVmean. Furthermore, the tumor-to-background ratio (TBR) was derived by dividing the SUVmax of tumor lesions by the SUVmax of adipose tissue, skeletal muscle, and blood pool. Results: Overall, 31 metastases were detected in five patients including lymph node metastases (n = 23), bone metastases (n = 4), lung metastases (n = 3), and a peritoneal metastasis (n = 1). In one patient, [68Ga]FAPI demonstrated significant uptake in the primary tumor located in the bladder wall. [68Ga]FAPI-PET/CT demonstrated significantly higher uptake compared to [18F]FDG PET/CT with higher mean SUVmax (8.2 vs. 4.6; p = 0.01). Furthermore, [68Ga]FAPI detected additional 30% (n = 9) lesions, missed by [18F]FDG. TBR demonstrated favorable uptake for [68Ga]FAPI in comparison to [18F]FDG. Significant differences were determined with regard to metastasis/blood pool ([68Ga]FAPI 5.3 vs [18F]FDG 1.9; p = 0.001). Conclusion: [68Ga]FAPI-PET/CT is a promising diagnostic radioligand for patients with bladder cancer. This first described analysis of FAP-ligand in bladder cancer revealed superiority over [18F]FDG in a small patient cohort. Thus, this so far assumed potential has to be confirmed and extended by larger and prospective studies. [ABSTRACT FROM AUTHOR]

Radiopharmaceutical therapies (RPTs) based on fibroblast activation protein (FAP) and FAP inhibitors (FAPIs) are a new option for progressive metastatic cancer in patients pretreated multiple times. To date, published in-human data refer to initial experiences with β-emitting 90 Y- and 177 Lu-based RPT. However, the short tumor retention time of FAPI ligands is considered a major limitation of FAPI RPT. Therefore, fractionated FAPI RPT with 213 Bi, an α-emitter with a half-life of 46 min, appears to be a promising FAPI RPT regimen. Here, we report on our initial experiences with regard to the feasibility, tolerability, and response of fractionated 213 Bi-FAPI-46 RPT. Methods: Six patients (4 women and 2 men) with progressive metastatic solid tumors (3 colon cancer, 1 anal cancer, 1 breast cancer, and 1 prostate cancer) aged 16-77 y were treated with a mean of 1,609 MBq of 213 Bi-FAPI-46, fractionated into 53 single applications (range, 5-12 RPT applications per patient; mean, 8.8 applications) over a period of up to 107 h per patient. Of the 6 patients, 4 patients received adjuvant treatment with pembrolizumab. 18 F-FDG (4 patients) and 68 Ga-FAPI-46 (5 patients) PET/CT scans were performed before and after RPT. PET images were assessed visually and by calculating total lesion glycolysis and total lesion FAPI. Results: RPT with 213 Bi-FAPI-46 was well tolerated without adverse side effects. In terms of visual response assessment, there was 1 partial response (16.7%), 1 patient with stable disease (16.7%), and 4 patients with progressive disease (66.7%). Concordantly, total lesion glycolysis and total lesion FAPI were decreased in the responding patient (not applicable and -24.3%, respectively), slightly decreased in the patient with stable disease (-10.6% and -5.9%, respectively), and increased in the 4 patients with progression (mean, +104.4% and +321.3%, respectively). Conclusion: Fractionated FAPI RPT with the short-half-life α-emitter 213 Bi-FAPI-46 is a promising approach that matches the pharmacokinetics of FAPI-46 better than the 177 Lu- or 90 Y-labeled compounds. In this pilot project, fractionated RPT with 213 Bi-FAPI-46 showed good clinical tolerability and even led to regressive or stable disease in the short term in 2 of 6 patients. Further studies with larger patient cohorts are required to evaluate the actual efficacy and long-term effects of this variant of FAPI RPT., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

68Ga-FAPI-PET/computed tomography (CT) is a novel PET/CT radiotracer particularly developed for oncologic imaging. Gynecologic malignancies comprise a broad spectrum of entities and, along with breast cancer, constitute cancers occurring exclusively or primarily, respectively, in women. Thus, a tracer designed not only for one but multiple malignancies has theoretic attractions. Even in comparison with 18F-FDG, the current standard oncologic tracer of nuclear medicine, 68Ga-FAPI, has demonstrated advantages in several tumors. As breast cancer, ovarian cancer, and cervical cancer are among the most common tumor types in women and are often accompanied by high morbidity as well as mortality rates, a reliable staging tool is paramount for optimal therapeutic management., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A growing family of 68 Ga-fibroblast activation protein inhibitor (FAPI) PET probes has shown promise in imaging a variety of medical conditions. 68 Ga-FAPI-46, in particular, has emerged as unique for both its diagnostic and its theranostic applications; however, the optimal timing of PET remains unclear. Therefore, we evaluated uptake at 3 time points after 68 Ga-FAPI-46 administration in a spectrum of tumor types. Methods: The cohort consisted of 43 patients with diverse cancer diagnoses undergoing 68 Ga-FAPI-46 PET/CT at 3 time points (10 min, 1 h, and 3 h). We determined the tracer uptake based on SUV mean and SUV max and on tumor-to-background-ratios (TBRs) (SUV max /SUV mean ). Results: There were 171 lesions in the 43 patients. Comparing all lesions at different time points, the mean SUV max was maximal at 10 min (8.2) and declined slightly at 1 h (8.15) and 3 h (7.6) after tracer administration. Similarly, the mean SUV max log still had a similar pattern in primary lesions at 10 min, 1 h, and 3 h ( n  = 30; 0.98, 1.01, and 0.98, respectively), lymph node metastases ( n  = 37; 0.82, 0.84, and 0.81, respectively), and distant metastases ( n  = 104; 0.81, 0.79, and 0.74, respectively). TBR also showed nonsignificant differences at the 3 times. Conclusion: 68 Ga-FAPI-46 PET/CT imaging revealed remarkably stable tumor and background uptake as determined by SUV metrics and maintained high TBRs within 3 h of injection. Thus, it may be possible to scan with 68 Ga-FAPI-46 within 10-20 min of injection, improving workflow and decreasing patient wait times. Confirmation of these findings in a larger cohort is under way., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Gallium 68 ( 68 Ga)-labeled fibroblast activation protein (FAP) inhibitor (FAPI) PET is based on the molecular targeting of the FAP, which is known to be highly expressed in the major cell population in tumor stroma, termed cancer-associated fibroblasts. Among many FAP-targeted radiopharmaceuticals developed so far, 68 Ga-FAPI exhibits rapid tracer accumulation in target lesions and low background signal, which results in excellent imaging features. FAPI PET can be integrated in the clinical workflow and enables the detection of small primary or metastatic lesions, especially in the brain, liver, pancreas, and gastrointestinal tract due to the low tracer accumulation in these organs. Moreover, the DOTA (1,4,7,10-tetraazacylclododecane-1,4,7,10-tetrayl tetraacetic acid) chelator in the molecular structure allows coupling of the FAPI molecules with therapeutic emitters such as yttrium 90 for theranostic applications. This review provides an overview of the state of the art in FAP imaging, summarizes the current knowledge of relevant cancer biology, and highlights the latest findings in the clinical use of 68 Ga-FAPI PET and other current FAPI tracers. Published under a CC BY 4.0 license.

68 Ga-labeled fibroblast activation protein (FAP) inhibitor ( 68 Ga-FAPI) PET targets 68 Ga-FAPI-positive activated fibroblasts and is a promising imaging technique for various types of cancer and nonmalignant pathologies. However, discrimination between malignant and nonmalignant 68 Ga-FAPI-positive lesions based on static PET with a single acquisition time point can be challenging. Additionally, the optimal imaging time point for 68 Ga-FAPI PET has not been identified yet, and different 68 Ga-FAPI tracer variants are currently used. In this retrospective analysis, we evaluate the diagnostic value of repetitive early 68 Ga-FAPI PET with 68 Ga-FAPI-02, 68 Ga-FAPI-46, and 68 Ga-FAPI-74 for malignant, inflammatory/reactive, and degenerative lesions and describe the implications for future 68 Ga-FAPI imaging protocols. Methods: Whole-body PET scans of 24 cancer patients were acquired at 10, 22, 34, 46, and 58 min after the administration of 150-250 MBq of 68 Ga-FAPI tracer molecules (8 patients each for 68 Ga-FAPI-02, 68 Ga-FAPI-46, and 68 Ga-FAPI-74). Detection rates and SUVs (SUV max and SUV mean ) for healthy tissues, cancer manifestations, and nonmalignant lesions were measured, and target-to-background ratios (TBR) versus blood and fat were calculated for all acquisition time points. Results: For most healthy tissues except fat and spinal canal, biodistribution analysis showed decreasing uptake over time. We analyzed 134 malignant, inflammatory/reactive, and degenerative lesions. Detection rates were minimally reduced for the first 2 acquisition time points and remained at a constant high level from 34 to 58 min after injection. The uptake of all 3 variants was higher in malignant and inflammatory/reactive lesions than in degenerative lesions. 68 Ga-FAPI-46 showed the highest uptake and TBRs in all pathologies. For all variants, TBRs versus blood constantly increased over time for all pathologies, and TBRs versus fat were constant or decreased slightly. Conclusion: 68 Ga-FAPI PET/CT is a promising imaging modality for malignancies and benign lesions. Repetitive early PET acquisition added diagnostic value for the discrimination of malignant from nonmalignant 68 Ga-FAPI-positive lesions. High detection rates and TBRs over time confirmed that PET acquisition earlier than 60 min after injection delivers high-contrast images. Additionally, considering clinical feasibility, acquisition at 30-40 min after injection might be a reasonable compromise. Different 68 Ga-FAPI variants show significant differences in time-dependent biodistributional behavior and should be selected carefully depending on the clinical setting., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Fibroblast activation protein (FAP) is ubiquitously present in healthy tissue, and additionally upregulated by cancer associated fibroblasts (CAFs) leading to high levels of FAP. Thus, neoplastic tissue, which is containing CAFs, characterized by a high presence of FAP. Moreover, in more than 90% of all epithelial tumors this phenomenon seems to occur, including many gynecological tumors, providing the foundation for a successful application of FAP-ligands. However, FAP upregulation, can also be initiated by benign conditions such as inflammation, hormonal-influence, and wound healing. Gynecological cancers seem to represent a field of interest for the utilization of FAPI-PET/CT to potentially improve staging, restaging and therapeutic management. First highly promising investigations demand further research in order to validate these preliminary findings., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Kidney fibrosis leads to a progressive reduction in kidney function ultimately resulting in kidney failure. Diagnostic tools to detect kidney fibrosis are all invasive in nature requiring kidney biopsies with subsequent histological validation. In this retrospective study, the diagnostic value of three different radiotracers for the noninvasive prediction of kidney fibrosis was analyzed, taking into account the glomerular filtration rate (GFR) and the intra-renal parenchymal radiotracer uptake., Methods: In 81 patients receiving either one of the following molecular imaging probes, [ 68  Ga]Ga-FAPI, [ 68  Ga]Ga-PSMA, or [ 68  Ga]Ga-DOTATOC, kidney function parameters were correlated with SUVmax and SUVmean of the renal parenchyma and background activity measured in lung parenchyma, myocardium, gluteal muscle, and the abdominal aorta. Patients were clustered according to their grade of chronic kidney disease (CKD), and a regression analysis and one-way ANOVA were conducted in this retrospective analysis., Results: We found a negative correlation between GFR and [ 68  Ga]Ga-FAPI uptake for both SUVmax and SUVmean values, whereas background activity showed no correlation with GFR. [ 68  Ga]Ga-DOTATOC and [ 68  Ga]Ga-PSMA did not correlate between CKD stage and intra-renal parenchymal radiotracer uptake. Only [ 68  Ga]Ga-PSMA background activity exhibited a positive correlation with GFR suggesting an unspecific binding/retention potentially due to longer circulation times., Conclusion: There is a significant negative correlation between renal parenchymal [ 68  Ga]Ga-FAPI uptake and GFR, which was not the case for [ 68  Ga]Ga-DOTATOC and [ 68  Ga]Ga-PSMA. This correlation suggests a specific binding of FAPI rather than a potential unspecific retention in the renal parenchyma, underlining the potential value of [ 68  Ga]Ga-FAPI for the noninvasive quantitative evaluation of kidney fibrosis., (© 2022. The Author(s).)

Abstract: Prostate-specific membrane antigen (PSMA) PET/CT is a highly reliable nuclear tracer for diagnostic imaging of prostate cancer. However, PSMA is also expressed by some nonprostatic tissues such as benign tumors, inflammatory processes, and malignant neoplasms. This case presents a patient with prostate cancer and follicular lymphoma undergoing PSMA PET/CT. Remarkably, both tumor entities were clearly detected in the scan. Yet, the 2 malignancies demonstrated rather different ranges in terms of SUVmax uptake values and therefore still enabled precise and accurate discrimination of prostate cancer and follicular lymphoma., Competing Interests: Conflicts of interest and sources of funding: Patent application for PSMA-1007 for F.L.G., U.H., and J.C. and for PSMA-617 for C.Kr. and U.H. F.L.G. is an advisor at SOFIE Biosciences, Telix, and ABX pharmaceutical. The remaining authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate fibroblast-activation-protein (FAP) expression in different clinical stages of prostate cancer (PC) with regards to utility of [ 68  Ga]Ga-FAPI-04 PET/CT imaging in patients with castration-resistant PC (CRPC)., Methods: Tissue microarrays (TMAs) were constructed from prostatic tissue from 94 patients at different stages of PC (primary PC, patients undergoing neoadjuvant androgen deprivation therapy, CRPC, and neuroendocrine PC (NEPC)) and were stained with anti-FAP monoclonal antibody. A positive pixel count algorithm (H-Index) was used to compare FAP expression between the groups. Additionally, three men with advanced CRPC or NEPC underwent [ 68  Ga]Ga-FAPI-04 PET/CT, and PET positivity was analyzed., Results: The mean H-index for benign tissue, primary PC, neoadjuvant androgen deprivation therapy before radical prostatectomy, CRPC, and NEPC was 0.018, 0.031, 0.042, 0.076, and 0.051, respectively, indicating a significant rise in FAP expression with advancement of disease. Corroborating these findings [ 68  Ga]Ga-FAPI-04 PET/CT was highly positive in men with advanced CRPC., Conclusion: Increased FAP tissue expression supports the use of FAP inhibitor (FAPI)-molecular theranostics in CRPC., (© 2021. The Author(s).)

Purpose: FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of 68 Ga-FAPI versus standard-of-care 18 F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers., Material and Methods: This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both 68 Ga-FAPI and 18 F-FDG PET/CT within a median time interval of 10 days (range 1-89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ)., Results: A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. 68 Ga-FAPI uptake in primary tumors and metastases was comparable to 18 F-FDG in most cases. The SUVmax was significantly lower for 68 Ga-FAPI than 18 F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, 68 Ga-FAPI TBRs were significantly higher than 18 F-FDG TBRs in some sites, including liver and bone metastases., Conclusion: Quantitative tumor uptake is comparable between 68 Ga-FAPI and 18 F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for 68 Ga-FAPI. Thus, 68 Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological 18 F-FDG uptake., (© 2021. The Author(s).)

Background: Local treatment of the primary or metastatic sites in urologic malignancies is promising when compared to systemic therapy alone, leading to the definition of a potentially curative oligometastatic state., Objectives: Comparison of imaging modalities regarding local and metastatic tumor sites in urologic cancers., Methods: Review of comparative trials addressing quality criteria of imaging modalities., Results: Depending on primary tumor and metastatic site, conventional imaging modalities such as computer tomography (CT) and bone scintigraphy still represent the standard of care in Germany. Due to superior quality criteria, hybrid-imaging techniques were widely adopted for oncological staging and particular due to the new PSMA-ligand (PSMA-PET/CT) in prostate cancer imaging. The development of new radioisotopes as well as their clinical application remains a focus of current research., Conclusions: High-quality diagnostic imaging modalities lay the groundwork for a precise definition of an oligometastatic state. By enabling treatment of the entire tumor burden, a delay of systemic therapy, longer progression-free survival, or even curative treatment may become achievable., (© 2021. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: 68 Ga-FAPI (fibroblast activation protein inhibitor) is a novel and highly promising radiotracer for PET/CT imaging. The aim of this retrospective analysis is to explore the potential of FAPI-PET/CT in gynecological malignancies. We assessed biodistribution, tumor uptake, and the influence of pre- or postmenopausal status on tracer accumulation in hormone-sensitive organs. Furthermore, a comparison with the current standard oncological tracer 18 F-FDG was performed in selected cases., Patients and Methods: A total of 31 patients (median age 59.5) from two centers with several gynecological tumors (breast cancer; ovarian cancer; cervical cancer; endometrial cancer; leiomyosarcoma of the uterus; tubal cancer) underwent 68 Ga-FAPI-PET/CT. Out of 31 patients, 10 received an additional 18 F-FDG scan within a median time interval of 12.5 days (range 1-76). Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean, and tumor-to-background ratio (TBR) was calculated (SUVmax tumor/ SUVmean organ). Moreover, a second cohort of 167 female patients with different malignancies was analyzed regarding their FAPI uptake in normal hormone-responsive organs: endometrium (n = 128), ovary (n = 64), and breast (n = 147). These patients were categorized by age as premenopausal (<35 years; n = 12), postmenopausal (>65 years; n = 68), and unknown menstrual status (35-65 years; n = 87), followed by an analysis of FAPI uptake of the pre- and postmenopausal group., Results: In 8 out of 31 patients, the primary tumor was present, and all 31 patients showed lesions suspicious for metastasis (n = 81) demonstrating a high mean SUVmax in both the primary (SUVmax 11.6) and metastatic lesions (SUVmax 9.7). TBR was significantly higher in 68 Ga-FAPI compared to 18 F-FDG for distant metastases (13.0 vs. 5.7; p = 0.047) and by trend for regional lymph node metastases (31.9 vs 27.3; p = 0.6). Biodistribution of 68 Ga-FAPI-PET/CT presented significantly lower uptake or no significant differences in 15 out of 16 organs, compared to 18 F-FDG-PET/CT. The highest uptake of all primary lesions was obtained in endometrial carcinomas (mean SUVmax 18.4), followed by cervical carcinomas (mean SUVmax 15.22). In the second cohort, uptake in premenopausal patients differed significantly from postmenopausal patients in endometrium (11.7 vs 3.9; p < 0.0001) and breast (1.8 vs 1.0; p = 0.004), whereas no significant difference concerning ovaries (2.8 vs 1.6; p = 0.141) was observed., Conclusion: Due to high tracer uptake resulting in sharp contrasts in primary and metastatic lesions and higher TBRs than 18 F-FDG-PET/CT, 68 Ga-FAPI-PET/CT presents a promising imaging method for staging and follow-up of gynecological tumors. The presence or absence of the menstrual cycle seems to correlate with FAPI accumulation in the normal endometrium and breast. This first investigation of FAP ligands in gynecological tumor entities supports clinical application and further research in this field., (© 2021. The Author(s).)

A fibroblast activation protein (FAP) is an atypical type II transmembrane serine protease with both endopeptidase and post-proline dipeptidyl peptidase activity. FAP is overexpressed in cancer-associated fibroblasts (CAFs), which are found in most epithelial tumors. CAFs have been implicated in promoting tumor cell invasion, angiogenesis and growth and their presence correlates with a poor prognosis. However, FAP can generally be found during the remodeling of the extracellular matrix and therefore can be detected in wound healing and benign diseases. For instance, chronic inflammation, arthritis, fibrosis and ischemic heart tissue after a myocardial infarction are FAP-positive diseases. Therefore, quinoline-based FAP inhibitors (FAPIs) bind with a high affinity not only to tumors but also to a variety of benign pathologic processes. When these inhibitors are radiolabeled with positron emitting radioisotopes, they provide new diagnostic and prognostic tools as well as insights into the role of the microenvironment in a disease. In this respect, they deliver additional information beyond what is afforded by conventional FDG PET scans that typically report on glucose uptake. Thus, FAP ligands are considered to be highly promising novel tracers that offer a new diagnostic and theranostic potential in a variety of diseases.

Fibroblast activation protein inhibitor emerges as a novel and highly promising agent for diagnostic and possibly theranostic application in various malignant and non-malignant diseases. FAPI impresses with its selective expression in several pathologies, ligand induced internalization, and presence in a large variety of malignancies. Current studies indicate that FAPI is equal or even superior to the current standard oncological tracer fluorodeoxyglucose in several oncological diseases. It seems to present lower background activity, stronger uptake in tumorous lesions and thus sharper contrasts. For improved comprehension of fibroblast activation, protein expression and clinicopathologic conditions, further studies are of essence., Competing Interests: Disclosure Drs. Haberkorn, Kratochwil and Giesel are named in a patent application (EP 18155420.5) for quinolone-based FAP-targeting agents for imaging and therapy in nuclear medicine. Drs. Kratochwil, Haberkorn and Giesel also have shares of a consultancy group for iTheranostics. Dr. Giesel is also advisor for ABX, SOFIE Biosciences and Telix pharmaceuticals. The other authors declare no potential conflict of interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)