Biodistribution and Dosimetry Evaluation of the Radiolabeled Somatostatin Receptor Antagonist 68Ga-DATA5m LM4 in Molecular Imaging of Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors Patients.

Purpose: This study aimed to assess the biodistribution and radiation dosimetry of 68Ga-DATA5m LM4 in patients with gastroenteropancreatic neuroendocrine tumors.

Patients And Methods: Eight patients (5 females and 3 males) with various gastroenteropancreatic neuroendocrine tumors were included in the study. Each patient underwent 3 whole-body PET scans at 10, 60, and 120 minutes after receiving an IV injection of approximately 162.

Exploring the FAP-Targeted Therapeutics for Adrenocortical Carcinoma: Choosing the Right Track.

Metastatic or recurrent adrenocortical carcinoma is a potentially lethal malignancy, presenting significant challenges in disease management owing to absence of effective systemic treatments. Significantly diminished survival rates necessitate rapid identification of specific molecules for the development of targeted therapeutics. Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts have been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment.

68 Ga-DOTA.SA.FAPi PET in Response Assessment After 177 Lu-Microspheres Selective Intra-arterial Radionuclide Therapy for Unresectable Hepatocellular Carcinoma.

We report a case of a 48-year-old man with recurrent hepatocellular carcinoma, who underwent FDG PET for restaging and demonstrated mildly tracer-avid arterial enhancing lesion in segment III (SUV max , 5.7). Owing to low FDG uptake, patient was planned for 68 Ga-SA.

Tailoring Fibroblast-Activation Protein Targeting for Theranostics: A Comparative Preclinical Evaluation of the Ga- and Lu-Labeled Monomeric and Dimeric Fibroblast-Activation Protein Inhibitors DOTA.SA.FAPi and DOTAGA.(SA.FAPi).

Background: FAP radiopharmaceuticals show promise for cancer diagnosis; however, their limited tumor residency hinders treatment. This study compared two FAPi derivatives, DOTA.SA.

Druglike, F-labeled PET Tracers Targeting Fibroblast Activation Protein.

Fibroblast activation protein (FAP) is a very reliable biomarker for tissue remodeling. FAP has so far mainly been studied in oncology, but there is growing interest in the enzyme in other diseases like fibrosis. Recently, FAP-targeting diagnostics and therapeutics have emerged, of which the so-called FAPIs are among the most promising representatives.

Head-to-Head Comparison of SSTR Antagonist [Ga]Ga-DATA-LM4 with SSTR Agonist [Ga]Ga-DOTANOC PET/CT in Patients with Well Differentiated Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Imaging Study.

Neuroendocrine tumors (NETs) are slow-growing tumors that express high levels of somatostatin receptors (SSTRs). Recent studies have shown the superiority of radiolabeled SSTR antagonists in theranostics compared to agonists. In this prospective study, we compared the diagnostic efficacy between [Ga]Ga-DOTANOC and [Ga]Ga-DATA-LM4 in the detection of primary and metastatic lesions in patients with well differentiated gastroenteropancreatic (GEP) NETs.

Ga-DOTA.SA.FAPi as a Versatile Diagnostic Probe for Various Epithelial Malignancies: A Head-to-Head Comparison with F-FDG.

Rationale And Objectives: Fibroblast Activation Protein (FAP) expressing cancer-associated fibroblasts has been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment. In this study, a squaric acid derivative DOTA.SA.

Next generation fibroblast activation protein (FAP) targeting PET tracers - The tetrazine ligation allows an easy and convenient way to F-labeled (4-quinolinoyl)glycyl-2-cyanopyrrolidines.

Small-molecular fibroblast activation protein inhibitor (FAPI)-based tracer have been shown to be promising Positron Emission Tomography (PET) Ga-labeled radiopharmaceuticals to image a variety of tumors including pancreatic, breast, and colorectal cancers, among others. In this study, we developed a novel F-labeled FAPI derivative. [F]6 was labeled using a synthon approach based on the tetrazine ligation.

Head-to-head comparison of [Ga]Ga-DOTA.SA.FAPi with [F]F-FDG PET/CT in radioiodine-resistant follicular-cell derived thyroid cancers.

Purpose: In the context of radioiodine-resistant follicular-cell derived thyroid cancers (RAI-R-FCTC), [F]F-FDG PET/CT serves as a widely used and valuable diagnostic imaging method. However, there is growing interest in utilizing molecular imaging probes that target cancer-associated fibroblasts (CAFs) as an alternative approach. This study sought to compare the diagnostic capabilities of [Ga]Ga-DOTA.

Translational assessment of a DATA-functionalized FAP inhibitor with facile Ga-labeling at room temperature.

Purpose: The present study aims at evaluating the preclinical and the clinical performance of [Ga]Ga-DATASA.FAPi, which has the advantage to be labeled with gallium-68 at room temperature.

Methods: [Ga]Ga-DATA.

Head-to-Head Comparison of [Ga]Ga-DOTA.SA.FAPi and [Ga]Ga-DOTANOC Positron Emission Tomography/Computed Tomography Imaging for the Follow-Up Surveillance of Patients with Medullary Thyroid Cancer.

A theranostic probe for accurate staging and treatment is crucial for the management of medullary thyroid cancers (MTCs). The abundance of stroma in most of thyroid cancers, including MTC, opens new avenues for selecting cancer-associated fibroblasts (CAFs) as new molecular imaging and therapeutic targets. [Ga]Ga-labeled fibroblast activation protein inhibitor (FAPi) molecules have gained importance as alternative molecular imaging agents in the imaging of thyroid cancers.

Head-to-Head Comparison between [Ga]Ga-DOTA.SA.FAPi and [F]F-FDG PET/CT Imaging in Patients with Breast Cancer.

This study aimed to compare the diagnostic performance of [Ga]Ga-DOTA.SA.FAPi with that of [F]F-FDG PET/CT in detecting primary and metastatic lesions of breast cancer.

Inhibition of Poly(ADP-ribose) Polymerase Sensitizes [Lu]Lu-DOTAGA.(SA.FAPi)-Mediated Radiotherapy in Triple-Negative Breast Cancer.

Fibroblast activation protein (FAP) is highly expressed in many tumor types and constitutes a promising target for tumor-specific delivery of therapeutic radionuclides. [Lu]Lu-DOTAGA.(SA.

[In]In/[Lu]Lu-AAZTA-LM4 SSTR-Antagonists in Cancer Theranostics: From Preclinical Testing to First Patient Results.

Aiming to expand the application of the SSTR-antagonist LM4 (DPhe-c[DCys-4Pal-DAph(Cbm)-Lys-Thr-Cys]-DTyr-NH) beyond [Ga]Ga-DATA-LM4 PET/CT (DATA, (6-pentanoic acid)-6-(amino)methy-1,4-diazepinetriacetate), we now introduce AAZTA-LM4 (AAZTA, 1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)]amino-6-[pentanoic-acid]perhydro-1,4-diazepine), allowing for the convenient coordination of trivalent radiometals of clinical interest, such as In-111 (for SPECT/CT) or Lu-177 (for radionuclide therapy). After labeling, the preclinical profiles of [In]In-AAZTA-LM4 and [Lu]Lu-AAZTA-LM4 were compared in HEK293-SSTR cells and double HEK293-SSTR/wtHEK293 tumor-bearing mice using [In]In-DOTA-LM3 and [Lu]Lu-DOTA-LM3 as references. The biodistribution of [Lu]Lu-AAZTA-LM4 was additionally studied for the first time in a NET patient.

68 Ga-DOTA.SA.FAPI as a Potential, Noninvasive Diagnostic Probe for Recurrent and Metastatic Adrenocortical Carcinoma : A Head-to-Head Comparison With 18F-FDG.

Metastatic or recurrent adrenocortical carcinoma (ACC) is a potentially fatal malignancy, which poses major challenges in disease management owing to lack of effective systemic therapies. The drastically reduced survival rates require prompt identification of selective molecules for development of targeted therapeutics. We evaluated the squaric acid containing FAPI derivative, DOTA.

From Automated Synthesis to In Vivo Application in Multiple Types of Cancer-Clinical Results with [Ga]Ga-DATA.SA.FAPi.

Radiolabeled FAPI (fibroblast activation protein inhibitors) recently gained attention as widely applicable imaging and potential therapeutic compounds targeting CAF (cancer-associated fibroblasts) or DAF (disease-associated fibroblasts in benign disorders). Moreover, the use of FAPI has distinct advantages compared to FDG (e.g.

First-in-Human Experience With 177Lu-DOTAGA.(SA.FAPi)2 Therapy in an Uncommon Case of Aggressive Medullary Thyroid Carcinoma Clinically Mimicking as Anaplastic Thyroid Cancer.

A 56-year-old man was diagnosed with calcitonin negative, plasma chromogranin A-positive, immunohistochemistry-negative, high-grade MTC (medullary thyroid cancer) behaving clinically like anaplastic thyroid cancer and presented with progressive disease after conventional therapies. A theranostic approach of 68Ga-DOTA.SA.

Fibroblast Activation Protein (FAP) targeting homodimeric FAP inhibitor radiotheranostics: a step to improve tumor uptake and retention time.

Several radiopharmaceuticals targeting fibroblast activation protein (FAP) based on the highly potent FAP inhibitor UAMC1110 are currently under investigation. Pre-clinical as well as clinical research exhibited the potential of these imaging agents. However, the monomeric small molecules seemed to have a short retention time in the tumor in combination with fast renal clearance.

First-In-Human Results on the Biodistribution, Pharmacokinetics, and Dosimetry of [Lu]Lu-DOTA.SA.FAPi and [Lu]Lu-DOTAGA.(SA.FAPi).

Recently, great interest has been gained regarding fibroblast activation protein (FAP) as an excellent target for theranostics. Several FAP inhibitor molecules such as [Ga]Ga-labelled FAPI-02, 04, 46, and DOTA.SA.

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

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.

Novel Fibroblast Activation Protein Inhibitor-Based Targeted Theranostics for Radioiodine-Refractory Differentiated Thyroid Cancer Patients: A Pilot Study.

This exploratory study was meant to assess clinical and safety data with a novel fibroblast activation protein inhibitor-based targeted theranostics as a salvage treatment option in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients who had progressed on tyrosine kinase inhibitors. Patients with metastatic RR-DTC who progressed on sorafenib/lenvatinib were prospectively recruited. If [Ga]Ga-DOTA.

Fibroblast activation protein inhibitor (FAPi) positive tumour fraction on PET/CT correlates with Ki-67 in liver metastases of neuroendocrine tumours.

Aim: Gallium-68-labelled inhibitors of the fibroblast activation protein (FAPi) enable positron emission tomography/computed tomography (PET/CT) imaging of fibroblast activation. We evaluated if [Ga]Ga-DATA5m.SA.

In Vitro Evaluation of the Squaramide-Conjugated Fibroblast Activation Protein Inhibitor-Based Agents AAZTA.SA.FAPi and DOTA.SA.FAPi.

Recently, the first squaramide-(SA) containing FAP inhibitor-derived radiotracers were introduced. DATA.SA.

Squaric Acid-Based Radiopharmaceuticals for Tumor Imaging and Therapy.

Targeting vectors bound to a chelator represent a significant fraction of radiopharmaceuticals used nowadays for diagnostic and therapeutic purposes in nuclear medicine. The use of squaramides as coupling units for chelator and targeting vector helps to circumvent the disadvantages of several common coupling methods. This review gives an overview of the use of squaric acid diesters (SADE) as linking agents.

AAZTA-squaramide ester competing with DOTA-, DTPA- and CHX-A″-DTPA-analogues: Promising tool for Lu-labeling of monoclonal antibodies under mild conditions.

Background: Combining the advantages of both cyclic and acyclic chelator systems, AAZTA (1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)]amino-6-methylperhydro-1,4-diazepine) is well suited for complexation of various diagnostic and therapeutic radiometals such as gallium-68, scandium-44 and lutetium-177 under mild conditions. Due to its specificity for primary amines and pH dependent binding properties, squaric acid (SA) represents an excellent tool for selective coupling of the appropriate chelator to different target vectors. Therefore, the aim of this study was to evaluate radiolabeling properties of the novel bifunctional AAZTA-SA being coupled to a model antibody (bevacizumab) in comparison to DOTA-SA, DTPA-p-Bn-SA and CHX-A″-DTPA-p-Bn-SA using the therapeutic nuclide lutetium-177.