Deescalated Ac-PSMA-617 Versus Lu/Ac-PSMA-617 Cocktail Therapy: A Single-Center Retrospective Analysis of 233 Patients.

The aim of this work is to evaluate our clinical real-world data obtained with Ac-PSMA-617 (AcPSMA), which were acquired under compassionate care regulations in patients with advanced-stage prostate cancer. The objective parameters that could be derived from this evaluation are compared with previous literature about AcPSMA and Lu-PSMA-617 (LuPSMA). The medical files of all patients who had received AcPSMA on an individual patient basis at the Heidelberg University Hospital since January 2014 were analyzed retrospectively.

Y post-radioembolization clinical assessment with whole-body Biograph Vision Quadra PET/CT: image quality, tumor, liver and lung dosimetry.

Purpose: Evaluation of Y liver radioembolization post-treatment clinical data using a whole-body Biograph Vision Quadra PET/CT to investigate the potential of protocol optimization in terms of scan time and dosimetry.

Methods: 17 patients with hepatocellular carcinoma with median (IQR) injected activity 2393 (1348-3298) MBq were included. Pre-treatment dosimetry plan was based on Tc-MAA SPECT/CT with Simplicit90Y™ and post-treatment validation with Quadra using Simplicit90Y™ and HERMIA independently.

Phantom study for Y liver radioembolization dosimetry with a long axial field-of-view PET/CT.

Purpose: The physical properties of yttrium-90 (Y) allow for imaging with positron emission tomography/computed tomography (PET/CT). The increased sensitivity of long axial field-of-view (LAFOV) PET/CT scanners possibly allows to overcome the small branching ratio for positron production from Y decays and to improve for the post-treatment dosimetry of Y of selective internal radiation therapy.

Methods: For the challenging case of an image quality body phantom, we compare a full Monte Carlo (MC) dose calculation with the results from the two commercial software packages Simplicit90Y and Hermes.

Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study.

Background: Actinium-225 (Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world.

Methods: This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa.

The Theranostic Optimization of PSMA-GCK01 Does Not Compromise the Imaging Characteristics of [Tc]Tc-PSMA-GCK01 Compared to Dedicated Diagnostic [Tc]Tc-EDDA/HYNIC-iPSMA in Prostate Cancer.

Purpose: Radiolabeled PSMA-ligands play a major role in today's nuclear medicine. Since approval of [Lu]Lu-PSMA-617 for therapy of metastatic prostate cancer, availability of Lu became bottleneck of supply due to the high demand. Recently, a theranostic PSMA-ligand, PSMA-GCK01, was developed which can be labeled either diagnostically with Tc or therapeutically with Re with both nuclides available from well-known generator systems.

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.

PSMA-GCK01: A Generator-Based Tc/Re Theranostic Ligand for the Prostate-Specific Membrane Antigen.

Prostate-specific membrane antigen (PSMA) theranostics have been introduced with Ga and Lu, the most used radionuclides. However, Re is a well-known generator-based therapeutic nuclide that completes a theranostic tandem with Tc and may offer an interesting alternative to the currently used radionuclides. In the present work, we aimed at the development of a PSMA-targeted Tc/Re theranostic tandem.

Static and Dynamic Ga-FAPI PET/CT for the Detection of Malignant Transformation of Intraductal Papillary Mucinous Neoplasia of the Pancreas.

Pancreatic ductal adenocarcinoma (PDAC) may arise from intraductal papillary mucinous neoplasms (IPMN) with malignant transformation, but a significant portion of IPMN remains to show benign behavior. Therefore, it is important to differentiate between benign IPMN and IPMN lesions undergoing malignant transformation. However, nonoperative differentiation by ultrasound, CT, MRI, and carbohydrate antigen 19-9 (CA19-9) is still unsatisfactory.

Repetitive Early Ga-FAPI PET Acquisition Comparing Ga-FAPI-02, Ga-FAPI-46, and Ga-FAPI-74: Methodologic and Diagnostic Implications for Malignant, Inflammatory/Reactive, and Degenerative Lesions.

Ga-labeled fibroblast activation protein (FAP) inhibitor (Ga-FAPI) PET targets 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 Ga-FAPI-positive lesions based on static PET with a single acquisition time point can be challenging. Additionally, the optimal imaging time point for Ga-FAPI PET has not been identified yet, and different Ga-FAPI tracer variants are currently used.

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.

Dosing Ac-DOTATOC in patients with somatostatin-receptor-positive solid tumors: 5-year follow-up of hematological and renal toxicity.

Purpose: The aim of this retrospective analysis is to estimate the most appropriate single cycle and cumulative doses of Ac-DOTATOC in patients treated for somatostatin-receptor-expressing cancers.

Methods: Ac-DOTATOC was administered to thirty-nine patients with various somatostatin-receptor-positive tumors. Baseline and follow-up Ga-DOTATOC PET/CT, lab tests, and renal scintigraphy were obtained.

Two Tumors, One Target: Preliminary Experience With 90Y-FAPI Therapy in a Patient With Metastasized Breast and Colorectal Cancer.

We report a patient with breast cancer (BC) diagnosed in 2009 with metachronous lymph node, liver, and bone metastases. In 2017, colorectal cancer with peritoneal metastases was additionally diagnosed and treated with 8 cycles of capecitabine due to its antitumor activity against both malignancies. At progression of both diseases, FAPI PET/CT demonstrated positive tumor targeting in BC-related metastases and colorectal cancer-related metastases.

FAP imaging in rare cancer entities-first clinical experience in a broad spectrum of malignancies.

Purpose:  Ga-FAPI (fibroblast activation protein inhibitor) is a rapidly evolving and highly promising radiotracer for PET/CT imaging, presenting excellent results in a variety of tumor entities, particularly in epithelial carcinomas. This retrospective analysis sought to evaluate the potential and impact of FAPI-PET/CT in rare cancer diseases with respect to improvement in staging and therapy, based on tracer uptake in normal organs and tumors.

Material And Methods: Fifty-five patients with rare tumor entities, defined by a prevalence of 1 person out of 2000 or less, received a  Ga-FAPI-PET/CT scan.

Nomograms to predict outcomes after Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study.

Background: Lutetium-177 (Lu) prostate-specific membrane antigen (Lu-PSMA) is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Predictors of outcomes after Lu-PSMA to enhance its clinical implementation are yet to be identified. We aimed to develop nomograms to predict outcomes after Lu-PSMA in patients with mCRPC.

The impact of the extent of the bone involvement on overall survival and toxicity in mCRPC patients receiving [Lu]Lu-PSMA-617: a WARMTH multicentre study.

Introduction: Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement.

Methods: The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [Lu]Lu-PSMA-617 and a follow-up of at least 6 months.

Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT.

Purpose: A high expression of fibroblast activation protein (FAP) was observed in multiple sarcomas, indicating an enormous potential for PET/CT using Ga-radiolabeled inhibitors of FAP (FAPI). Therefore, this retrospective study aimed to evaluate the role of the novel hybrid imaging probe for sarcomas as a first clinical evaluation.

Methods: A cohort of 15 patients underwent Ga-FAPI-PET/CT for staging or restaging.

Ga-FAPI-PET/CT improves diagnostic staging and radiotherapy planning of adenoid cystic carcinomas - Imaging analysis and histological validation.

Background: Adenoid cystic carcinomas (ACCs) are rare epithelial tumors mostly situated in the head and neck region and characterized by infiltrative growth. The tumor stroma of ACCs includes cancer-associated fibroblasts (CAFs) expressing Fibroblast Activation Protein (FAP), a new target for positron emission tomography (PET) imaging. Here we describe the value of PET/ computed tomography (PET/CT) imaging using Ga-labelled FAP-Inhibitors (Ga-FAPI-PET/CT) and their clinical potential for staging and radiotherapy planning in 12 ACC patients (7 primary, 5 recurrent).

The role of combined ion-beam radiotherapy (CIBRT) with protons and carbon ions in a multimodal treatment strategy of inoperable osteosarcoma.

Background: To investigate the role of combined ion-beam radiotherapy (CIBRT) with protons and carbon ions in a multimodal treatment strategy of inoperable osteosarcoma; final analysis of a one-armed, single center phase I/II trial.

Methods: Between August 2011 until September 2018, 20 patients with primary (N = 18), metastatic (N = 3), or recurrent (N = 2) inoperable pelvic (70%) or craniofacial (30%) osteosarcoma were treated with protons up to 54 Gy (RBE) and a carbon ion boost of 18 Gy (RBE) and followed until May 2019. A Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was performed before CIBRT in search for a prognostic factor.

Impact of Ga-FAPI PET/CT Imaging on the Therapeutic Management of Primary and Recurrent Pancreatic Ductal Adenocarcinomas.

Pancreatic ductal carcinoma (PDAC) is a highly lethal cancer, and early detection and accurate staging are critical to prolonging survival. PDAC typically has a prominent stroma including cancer-associated fibroblasts that express fibroblast activation protein (FAP). FAP is a new target molecule for PET imaging of various tumors.

Efficacy and Safety of Lu-labeled Prostate-specific Membrane Antigen Radionuclide Treatment in Patients with Diffuse Bone Marrow Involvement: A Multicenter Retrospective Study.

The Lu-labeled prostate-specific membrane antigen (LuPSMA) radionuclide therapy for metastatic castration-resistant prostate cancer is under investigation in a phase III trial (VISION: NCT03511664). However, patients with diffuse bone involvement, diagnosed with a "superscan" by bone scintigraphy at baseline, were excluded due to a lack of efficacy and safety data. We therefore aimed to investigate the feasibility of LuPSMA in patients with diffuse bone marrow involvement on baseline PSMA-targeted positron emission tomography.

Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [Lu]Lu-PSMA-617. A WARMTH multicenter study (the 617 trial).

Introduction: The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the "617 trial") to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with Lu-PSMA-617.

Materials And Methods: The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated.