Fibroblast activation protein inhibitor PET/CT as an emerging diagnostic modality in interstitial lung disease and other fibrotic conditions.

Interstitial lung diseases (ILD) encompass a wide range of disorders characterized by alveolar inflammation and fibrotic tissue remodeling, marked by significant morbidity and mortality. Systemic sclerosis (SSc), among other connective tissue diseases, is a frequent cause of ILD. Assessment of pulmonary fibrosis is frequently constrained by the delayed manifestations of profibrotic activation of fibroblasts, which results in late macroscopic alterations detectable by standard imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) scans.

The Predictive Role of Metabolic Volume Segmentation Compared to Semiquantitative PET Parameters in Diagnosis of LVAD Infection using [F]FDG Imaging.

Purpose: Left ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy. Yet device infection represents a major lethal complication, warranting a multi-step, complex therapy approach including an urgent device exchange or heart transplantation. Still, timely diagnosis of site and extent of VAD-specific infection for a proper therapy planning poses challenges in regular clinical care.

[FAPI-PET-CT for quantification of the tissue response in rheumatic diseases].

Fibroblast activation protein (FAP) is mainly found on the surface of activated fibroblasts but is not expressed on the surface of inactive fibroblasts. Selective FAP inhibitors (FAPI), which are coupled to a radioactive tracer, can be used to quantify profibrotic and proinflammatory fibroblasts in patients using FAPI positron emission tomography (PET) computed tomography (CT). Following initial applications in neoplastic diseases, FAPI-PET/CT is also increasingly being applied in rheumatological diseases.

Radiomolecular Theranostics With Fibroblast-Activation-Protein Inhibitors and Peptides.

The advancement of theranostics, which combines therapeutic and diagnostic capabilities in oncology, has significantly impacted cancer management. This review explores fibroblast activation protein (FAP) expression in the tumor microenvironment (TME) and its association with various malignancies, highlighting its potential as a theranostic marker for PET/CT imaging using FAP-targeted tracers and for FAP-targeted radiopharmaceutical therapy. We examine the development and clinical applications of FAP inhibitors (FAPIs) and peptides, providing insights into their diagnostic accuracy, initial therapeutic efficacy, and clinical impact across diverse cancer types, as well as the synthesis of novel FAP-targeted ligands.

Initial results with [F]FAPI-74 PET/CT in idiopathic pulmonary fibrosis.

Unlabelled: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis. Ga-labeled FAP ligands exhibited highly promising results due to the crucial role of activated fibroblasts in fibrosis imaging of the lung. However, F-labeled FAP ligands might provide qualitatively much higher imaging results with accompanying economic benefits due to large-scale production.

Head-to-Head Intra-Individual Comparison of Biodistribution and Tumor Uptake of [F]FAPI-74 with [F]FDG in Patients with PDAC: A Prospective Exploratory Study.

Background: Radiolabeled fibroblast activation protein (FAP) ligands, a novel class of tracers for PET/CT imaging, have demonstrated very promising results in various oncological, as well as in some benign, diseases with long-term potential to supplant the current pan-cancer agent [F]FDG in some cancer types. Pancreatic ductal carcinoma (PDAC) belongs to the group of epithelial malignancies with a strong so-called "desmoplastic reaction", leading to a prominent tumor stroma with cancer-associated fibroblasts that exhibit a marked overexpression of fibroblast activation protein (FAP). The first clinical experiences in PDAC with Ga-labeled FAP ligands suggested superior sensitivity to [F]FDG.

Intra-Individual Comparison of Physiologic [Ga]Ga-PSMA-11 and [F]PSMA-1007 Uptake in Ganglia in Patients with Prostate Cancer: A Retrospective, Monocentric Analysis.

Background: Several studies indicate, particularly in the case of [18F]PSMA-1007, a relatively high rate of detection of ganglia in PSMA PET imaging. Ganglia are an integral part of the sympathetic portion of the autonomous nervous system. To date, no studies have directly compared [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 ganglionic uptake intra-individually and analyzed the underlying molecular and physical mechanisms of different detection rates.

Initial Evaluation of [F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions.

The F-labeled fibroblast activation protein inhibitor (FAPI) [F]FAPI-74 has the benefit of a higher synthetic yield and better image resolution than Ga-labeled FAPI. We preliminarily evaluated the diagnostic performance of [F]FAPI-74 PET in patients with various histopathologically confirmed cancers or suspected malignancies. We enrolled 31 patients (17 men and 14 women) with lung cancer ( = 7), breast cancer ( = 5), gastric cancer ( = 5), pancreatic cancer ( = 3), other cancers ( = 5), and benign tumors ( = 6).

Fibroblast Activation Protein Inhibitor Theranostics: Early Clinical Translation.

Fibroblast activation protein (FAP)-targeted radioligand therapy offers a possibility of a novel cancer therapeutic strategy, aiming at tumor stroma1. Early clinical translations of FAP-tracers occurred as early as in the 1990s using antibodies, without substantial achievement further than the clinical phase II trial. The essential step toward the theranostic approach, with a conceptual combination of diagnostic and therapeutic emitters in a specific tracer, began with the implementation of small-molecule FAP-enzyme inhibitors (FAPI) in 2018.

The Diagnostic Value of Fibroblast Activation Protein Imaging in Hepatocellular Carcinoma and Cholangiocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with worldwide high incidence and mortality. In more than 90% of cases, HCC arise from a cirrhotic liver that is mostly induced by viral diseases and especially in developed countries alcoholic steatohepatitis and non-alcoholic steatohepatitis. In contrast, cholangiocellular carcinoma (CCC) is a very rare cancer entity with a high mortality due to insidious onset.

[Breakeven Analysis for Imaging Devices: Basic Introduction with Presentation of a User-Friendly Tool for in-clinic Calculation Using PET/CT as an Example].

Background: Imaging devices such as PET/CT are becoming increasingly important in view of the growing range of innovative nuclear medicine diagnostic procedures. Since the procurement and commissioning as well as the ongoing operation of imaging devices leads to comparatively high costs, it is of great interest for clinics and practices to know the number of scans from which the (planned) device operation leads to a profit. In the following, we will introduce the breakeven point analysis and present a calculation tool that users in nuclear medicine clinics and practices can use in everyday operations using PET/CT as an example.

FAPI PET: Fibroblast Activation Protein Inhibitor Use in Oncologic and Nononcologic Disease.

Gallium 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, 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.

Three-Time-Point PET Analysis of Ga-FAPI-46 in a Variety of Cancers.

A growing family of Ga-fibroblast activation protein inhibitor (FAPI) PET probes has shown promise in imaging a variety of medical conditions. 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 Ga-FAPI-46 administration in a spectrum of tumor types.

Primary thyroid gland myxofibrosarcoma: a case report and review of the literature.

Background: Myxofibrosarcoma is a common soft tissue sarcoma of the extremities, which occurs very rarely in the thyroid gland.

Case Presentation: We report the case of a 61-year-old male who presented with a swelling of the left side of the neck and a newly emerged hoarseness. Ultrasound depicted a hypoechoic thyroid nodule with microcalcifications that was highly suspicious for malignancy.

Advancement and Future Perspective of FAPI PET/CT In Gynecological Malignancies.

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.

A Role of Non-FDG Tracers in Lung Cancer?

Since the introduction of PET/CT hybrid imaging about two decades ago the landscape of oncological imaging has fundamentally changed, opening a new era of molecular imaging with emphasis on functional characterization of biological processes such as metabolism, cellular proliferation, hypoxia, apoptosis, angiogenesis and immune response. The most commonly assessed functional hallmark of cancer is the increased metabolism in tumor cells due to well-known Warburg effect, because of which FDG has been the most employed radiotracer, the so-called pan-cancer agent, in oncological imaging. However, several limitations such as low specificity and low sensitivity for several histopathological forms of lung cancer as well as high background uptake in the normal tissue of FDG imaging lead to numerous serious pitfalls.

Serotonergic Modulation of Nigrostriatal and Mesolimbic Dopamine and Motor/Exploratory Behaviors in the Rat.

The 5-HT receptor (R) is known to modulate dopamine (DA) release in the mammalian brain. Altanserin (ALT) and 2,5-dimethoxy-4-iodoamphetamine (DOI) act as 5-HTR antagonist and agonist, respectively. In the present study, we assessed the effects of ALT and DOI on motor and exploratory behaviors and on DR binding in the rat brain with imaging methods.

One-pot and one-step automated radio-synthesis of [F]AlF-FAPI-74 using a multi purpose synthesizer: a proof-of-concept experiment.

Background: Fibroblast activation protein (FAP) is overexpressed in the stroma of many types of cancer. [F]AlF-FAPI-74 is a positron emission tomography tracer with high selectivity for FAP, which has already shown high accumulation within human tumors in clinical studies. However, [F]AlF-FAPI-74 radiosynthesis has not been optimized using an automated synthesizer.

GABAergic and glutamatergic effects on nigrostriatal and mesolimbic dopamine release in the rat.

In this review, a series of experiments is presented, in which γ-amino butyric acid (GABA)ergic and glutamatergic effects on dopamine function in the rat nigrostriatal and mesolimbic system was systematically assessed after pharmacological challenge with GABAA receptor (R) and and N-methyl d-aspartate (NMDA)R agonists and antagonists. In these studies, [123I]iodobenzamide binding to the D2/3R was mesured in nucleus accumbens (NAC), caudateputamen (CP), substantia nigra/ventral tegmental area (SN/VTA), frontal (FC), motor (MC) and parietal cortex (PC) as well as anterior (aHIPP) and posterior hippocampus (pHIPP) with small animal SPECT in baseline and after injection of either the GABAAR agonist muscimol (1 mg/kg), the GABAAR antagonist bicuculline (1 mg/kg), the NMDAR agonist d-cycloserine (20 mg/kg) or the NMDAR antagonist amantadine (40 mg/kg). Muscimol reduced D2/3R binding in NAC, CP, SN/VTA, THAL and pHIPP, while, after amantadine, decreases were confined to NAC, CP and THAL.

Epigenetic alterations of a novel antioxidant gene predispose susceptible individuals to increased risk of esophageal cancer.

Esophageal squamous cell carcinoma (ESCC) occurs with the highest frequency in China, especially in the high-risk Northern Chinese. Recent studies have reported that is significantly downregulated in non-tumor (NT) esophageal tissues from familial ESCC patients compared with those from sporadic ESCC. However, the mechanism of how regulates familial ESCC remains unknown.