The SCARLET trial: a prospective phase II study of somatostatin receptor imaging for potential radiotheranostic application in patients with relapsing and refractory multiple myeloma.

Purpose: This phase II study investigates the expression of somatostatin receptors (SSTR) in relapsing and refractory multiple myeloma (rrMM) patients for potential radiotheranostic application.

Methods: Seventeen triple-class exposed rrMM patients who demonstrate [F]F-FDG avidity were prospectively included. Patients underwent a [Ga]Ga-DOTATATE PET/CT within 4 weeks after [F]F-FDG PET/CT, which was performed as part of the standard workup.

First-in-human experience of radiopharmaceutical therapy with [Lu]Lu-DOTATATE in patients with advanced multiple myeloma.

Radiotheranostics using somatostatin receptor (R)-targeted agents has transformed the management of neuroendocrine tumors, yet its application in other oncological entities remains unexplored. Here, we report the firsSt-inST-human use of [Lu]Lu-DOTATATE in two patients with advanced, triple-class refractory multiple myeloma, selected based on dual imaging with [Ga]Ga-DOTATATE and [F]F-FDG PET/CT. Both patients received standard activities of [Lu]Lu-DOTATATE, resulting in favourable safety profiles and improved quality of life.

[F]FDG Metabolic Tumor Volume as a Prognostic Marker in Neuroendocrine Neoplasm: A Multicenter Study.

[F]FDG PET/CT avidity predicts higher-grade disease and worse prognosis in patients with metastatic neuroendocrine neoplasm. However, there is less evidence regarding the role of [F]FDG-avid tumor volume in predicting prognosis. We planned to determine whether metabolic tumor volume (MTV) on [F]FDG PET/CT predicts prognosis in patients with advanced gastroenteropancreatic neuroendocrine neoplasm (GEPNEN).

Development and Validation of an F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography-Based Imaging Score to Predict 12-Week Life Expectancy in Advanced Chemorefractory Colorectal Cancer.

Purpose: Managing chemorefractory metastatic colorectal cancer (mCRC) requires a meticulous equilibrium between the efficacy and toxicity of interventions, a task compounded by the constrained life expectancy of the patient. While existing prognostic tools, such as the Colon Life nomogram, primarily focus on general patient conditions or a single diagnostic modality, they do not fully integrate the potential predictive value of multimodal data. This study aims to develop and validate an Imaging Score, integrating clinical and imaging features derived from whole-body F-fluorodeoxyglucose (F-FDG) positron emission tomography-computed tomography (PET-CT), predicting death probability within 12 weeks from treatment initiation for refractory disease.

Secondary Pulmonary Hypertrophic Osteoarthropathy Detected on [68Ga]Ga-FAPI-46 PET/CT.

A 55-year-old man presented with arthralgia, digital clubbing, and pitting edema. A suspicious pulmonary mass showed high tracer uptake on both [18F]FDG and [68Ga]Ga-FAPI-46 PET/CT. Remarkably, FAPI PET revealed a diffuse periosteal tracer uptake of the long bones, highly suggestive for hypertrophic osteoarthropathy.

FAPI PET in the Management of Lung Tumors.

Fibroblast activation protein (FAP), selectively expressed on activated fibroblasts in proliferating tissues, is emerging as a promising target in oncology. In lung cancer, the leading cause of cancer-related deaths worldwide, [F]FDG PET/CT has set the bar high and earned widespread recognition in clinical guidelines for its essential role in staging and follow-up. Yet, FAP-targeted imaging agents like FAPI PET/CT have demonstrated significant potential due to their high tumor specificity, rapid tracer uptake, and low background activity.

Evolution of dosimetric parameters through PRRT and potential impact on clinical practice: data from the prospective phase II LUMEN study.

Background: Peptide receptor radionuclide therapy (PRRT) with [Lu]Lu-DOTA-TATE has emerged as a promising treatment for gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Its treatment protocol is currently standardised for all patients, resulting in different patient outcomes. This study investigates the variability of tumours and organs-at-risk (kidneys and red marrow) dosimetric parameters across treatment cycles in patients with pancreatic and intestinal NETs.

Phosphaturic mesenchymal tumor demonstrated by Ga-DOTATATE PET/CT in a patient: a case report.

Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome caused by abnormally high levels of fibroblast growth factor 23 (FGF-23), most commonly produced and secreted by small phosphaturic mesenchymal tumors (PMT). These tumors can show various anatomic locations throughout soft tissue and bone. The presence of the tumor itself rarely causes symptoms.

Results from a phase I study of 4--[131I]iodo-phenylalanine ([I]IPA) with external radiation therapy in patients with recurrent glioblastoma (IPAX-1).

Background: Glioblastoma (GBM), the most common malignant brain tumor, is associated with devastating outcomes. IPAX-1 was a multicenter, open-label, single-arm phase I study to evaluate carrier-added 4--[I]iodo-phenylalanine ([I]IPA) plus external radiation therapy (XRT) in recurrent GBM.

Methods: A total of 10 adults with recurrent GBM who had received first-line debulking surgery plus radio-chemotherapy, were randomized to a single-dose regimen (1f; I-IPA 2 GBq before XRT); a fractionated parallel dose regimen (3f-p; 3 I-IPA 670 MBq fractions, in parallel with second-line XRT), or a fractionated sequential dose regimen (3f-s; 3 I-IPA 670 MBq fractions before and after XRT).

177 Lu-DOTATATE PRRT Safety and Organ-at-Risk Dosimetry in Patients With Gastroenteropancreatic Neuroendocrine Tumors : Data From the Prospective Phase 2 LUMEN Study.

Purpose: The aim of this study was to assess the association among toxicity, dosimetry of organs-at-risk, and disease progression in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with 177 Lu-DOTATATE.

Patients And Methods: Thirty-seven patients with GEP-NETs underwent 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in a single-arm, prospective, phase 2 study, where patients were followed up with blood tests, isotopic glomerular filtration rate (iGFR), and imaging examinations (CT/MRI and PET) every 6 months until disease progression. Adverse events (AEs) graded per CTCAEv4.

Optimal [F]FDG PET/CT Cutoff for Pathologic Complete Response in HER2-Positive Early Breast Cancer Patients Treated with Neoadjuvant Trastuzumab and Pertuzumab in the PHERGain Trial.

The PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy deescalation in human epidermal growth factor receptor 2 (HER2)-positive, invasive, operable breast cancer with at least 1 breast lesion evaluable by [F]FDG PET/CT. [F]FDG PET/CT responders were defined as patients with an SUV reduction (ΔSUV) of at least 40% in all of their target lesions after 2 cycles of trastuzumab and pertuzumab (HP) (with or without endocrine therapy). In total, 227 of 285 patients (80%) included in the HP arm showed a predefined metabolic response and received a total of 8 cycles of HP (with or without endocrine therapy).

Impact of scatter correction on personalized dosimetry in selective internal radiotherapy using Ho-PLLA: a single-center study including Monte-Carlo simulation, phantom and patient imaging.

Background: Developments in transarterial radioembolization led to the conception of new microspheres loaded with holmium-166 (Ho). However, due to the complexity of the scatter components in Ho single photon emission computed tomography (SPECT), questions about image quality and dosimetry are emerging. The aims of this work are to investigate the scatter components and correction methods to propose a suitable solution, and to evaluate the impact on image quality and dosimetry including Monte-Carlo (MC) simulations, phantom, and patient data.

Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma or a Metaphor for Heterogeneity: From Single-Cell Analysis to Whole-Body Imaging.

Pancreatic ductal adenocarcinoma (PDAC) represents a formidable challenge due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) in PDAC, characterized by intense stromal desmoplastic reactions and a dominant presence of cancer-associated fibroblasts (CAFs), significantly contributes to therapeutic resistance. However, within the heterogeneous CAF population, fibroblast activation protein (FAP) emerges as a promising target for Gallium-68 FAP inhibitor positron emission tomography (Ga68FAPI-PET) imaging.

Molecular imaging predicts lack of T-DM1 response in advanced HER2-positive breast cancer (final results of ZEPHIR trial).

Efficacy of the human epidermal growth factor receptor (HER)2-targeting trastuzumab emtansine (T-DM1) in breast cancer (BC) relies on HER2 status determined by immunohistochemistry or fluorescence in-situ hybridization. Heterogeneity in HER2 expression, however, generates interest in "whole-body" assessment of HER2 status using molecular imaging. We evaluated the role of HER2-targeted molecular imaging in detecting HER2-positive BC lesions and patients unlikely to respond to T-DM1.

[F]FDG PET/CT-Avid Discordant Volume as a Biomarker in Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicenter Study.

[F]FDG PET/CT and [Ga]Ga-DOTATATE PET/CT are both used to predict tumor biology in neuroendocrine neoplasms. Although the presence of discordant ([F]FDG-avid/non-[Ga]Ga-DOTATATE-avid) disease predicts poor prognosis, the significance of the volume of such discordant disease remains undetermined. The aim of this study is to investigate discordant tumor volume as a potential biomarker in patients with advanced gastroenteropancreatic neuroendocrine neoplasms (GEPNENs).

Prediction of Lu-DOTATATE PRRT Outcome Using Multimodality Imaging in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Results from a Prospective Phase II LUMEN Study.

Our objective was to predict the outcome of peptide receptor radionuclide therapy (PRRT) using multimodality imaging and tumor dosimetry on gastroenteropancreatic neuroendocrine tumor (GEP-NET) lesions and patients. This prospective study included patients with progressive GEP-NETs. Treatment consisted of 4 cycles of 7.

Quantitative Lu SPECT/CT imaging for personalized dosimetry using a ring-shaped CZT-based camera.

Background: Dosimetry after radiopharmaceutical therapy with Lu (Lu-RPT) relies on quantitative SPECT/CT imaging, for which suitable reconstruction protocols are required. In this study, we characterized for the first time the quantitative performance of a ring-shaped CZT-based camera using two different reconstruction algorithms: an ordered subset expectation maximization (OSEM) and a block sequential regularized expectation maximization (BSREM) combined with noise reduction regularization. This study lays the foundations for the definition of a reconstruction protocol enabling accurate dosimetry for patients treated with Lu-RPT.

PSMA PET/CT for Response Assessment and Overall Survival Prediction in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors.

We aimed to evaluate the role of prostate-specific membrane antigen (PSMA) PET/CT for response assessment and outcome prediction in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor pathway inhibitors (ARPIs), including abiraterone acetate or enzalutamide. We retrospectively analyzed 30 ARPI-treated mCRPC patients who underwent Ga-PSMA-11 PET/CT within 8 wk before (baseline) and 12 ± 4 wk after treatment initiation. Total PSMA tumor volume was calculated using the fixed threshold method (SUV ≥ 3).

FAP-targeted PET imaging in gastrointestinal malignancies: a comprehensive review.

F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) plays a crucial role in tumour diagnosis, staging, and therapy response evaluation of various cancer types and has been a standard imaging modality used in clinical oncology practice for many years. However, it has certain limitations in evaluating some particular gastrointestinal cancer types due to low FDG-avidity or interphering physiological background activity. Fibroblast activation protein (FAP), a protein of the tumour microenvironment, is overexpressed in a wide range of cancers which makes it an attractive target for both tumour imaging and therapy.

Tumor Volume on PSMA PET as a Prognostic Biomarker in Prostate Cancer Patients Treated With Cabazitaxel.

Purpose: The aim of this study was to evaluate the prognostic value of 68 Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT in metastatic castration-resistant prostate cancer patients receiving second-line chemotherapy with cabazitaxel.

Methods: All patients with metastatic castration-resistant prostate cancer who underwent a PSMA PET/CT within 8 weeks before initiating the cabazitaxel treatment were retrospectively evaluated. The whole-body PSMA total tumor volume (PSMA-TV) was measured for each patient.

Peering through the PSMA PET Lens: The Role of the European Association of Urology Biochemical Recurrence Risk Groups after Radical Prostatectomy.

(1) Background: The European Association of Urology (EAU) biochemical recurrence (BCR) risk grouping relies on data from historical cohorts that used conventional imaging techniques. In the era of PSMA PET/CT, we compared the patterns of positivity in the two risk groups and provided insight into positivity predictive factors. (2) Methods: Data from 1185 patients who underwent Ga-PSMA-11PET/CT for BCR was analyzed, out of which 435 patients treated initially treated by radical prostatectomy were included in the final analysis.

Disturbing the Redox Balance Using Buthionine Sulfoximine Radiosensitized Somatostatin Receptor-2 Expressing Pre-Clinical Models to Peptide Receptor Radionuclide Therapy with Lu-DOTATATE.

Peptide receptor radionuclide therapy with Lu-DOTATATE improves the outcome of patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Nevertheless, stable disease has been the main response pattern observed, with some rare complete responses. Lu-177 exerts about two-thirds of its biological effects via the indirect effects of ionizing radiation that generate reactive oxygen species, eventually leading to oxidative damage and cell death.