Patient outcomes following a response biomarker-guided approach to treatment using 177Lu-PSMA-I&T in men with metastatic castrate-resistant prostate cancer (Re-SPECT).

Background: LuPSMA is an effective treatment in metastatic castrate-resistant prostate cancer with trials adopting a standardised dose interval. Adjusting treatment intervals utilising early response biomarkers may improve patient outcomes.

Objective: This study evaluated progression-free survival (PFS) and overall survival (OS) based on treatment interval adjustment utilising LuPSMA 24-h SPECT/CT (Lu-SPECT) and early prostate-specific antigen (PSA) response.

Evaluation of Lu-PSMA-617 SPECT/CT Quantitation as a Response Biomarker Within a Prospective Lu-PSMA-617 and NOX66 Combination Trial (LuPIN).

Lu-PSMA-617 is an effective and novel treatment in metastatic castration-resistant prostate cancer (mCRPC). Our ability to assess response rates and therefore efficacy may be improved using predictive tools. This study investigated the predictive value of serial Lu-PSMA-617 SPECT/CT (Lu SPECT) imaging in monitoring treatment response.

The Prognostic Value of Posttreatment Ga-PSMA-11 PET/CT and F-FDG PET/CT in Metastatic Castration-Resistant Prostate Cancer Treated with Lu-PSMA-617 and NOX66 in a Phase I/II Trial (LuPIN).

Lu-PSMA-617 therapy has shown high prostate-specific antigen (PSA) response rates in men with metastatic castration-resistant prostate cancer. However, early treatment resistance is common. This LuPIN substudy aimed to determine the prognostic value of posttreatment quantitative PET for PSA progression-free survival (PFS) and overall survival (OS) with Lu-PSMA-617 therapy.

Fully Automated Ga-Labeling and Purification of Macroaggregated Albumin Particles for Lung Perfusion PET Imaging.

Lung PET/CT is a promising imaging modality for regional lung function assessment. Our aim was to develop and validate a fast, simple, and fully automated GMP compliant [Ga]Ga-MAA labeling procedure, using a commercially available [Tc]Tc-MAA kit, a direct gallium-68 eluate and including a purification of the [Ga]Ga-MAA. The synthesis parameters (pH, heating temperature) were manually determined.

Lu-PSMA-617 and Idronoxil in Men with End-Stage Metastatic Castration-Resistant Prostate Cancer (LuPIN): Patient Outcomes and Predictors of Treatment Response in a Phase I/II Trial.

Lu-PSMA-617 is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC). However, treatment resistance occurs frequently, and combination therapies may improve outcomes. We report the final safety and efficacy results of a phase I/II study combining Lu-PSMA-617 with idronoxil (NOX66), a radiosensitizer, and examine potential clinical, blood-based, and imaging biomarkers.

Utility of Ga-DOTA-Exendin-4 positron emission tomography-computed tomography imaging in distinguishing between insulinoma and nesidioblastosis in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia.

Background: Because management is very different, it is important to differentiate between small focal insulinomas and diffuse pancreatic dysplasia (nesidioblastosis) in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia (EHH). Most insulinomas highly express glucagon-like peptide-1 receptors enabling positron emission tomography-computed tomography imaging with its radiolabelled analogue; Ga-DOTA-Exendin-4 (Exendin).

Aim: To determine: (i) the utility of Exendin in EHH patients in a clinical setting; and (ii) whether the degree of Exendin uptake differentiates non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) from post-gastric bypass hypoglycaemia (PGBH).

Single-arm prospective interventional study assessing feasibility of using gallium-68 ventilation and perfusion PET/CT to avoid functional lung in patients with stage III non-small cell lung cancer.

Background: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy.

Synthesis of [F]F-γ-T-3, a Redox-Silent γ-Tocotrienol (γ-T-3) Vitamin E Analogue for Image-Based In Vivo Studies of Vitamin E Biodistribution and Dynamics.

Vitamin E, a natural antioxidant, is of interest to scientists, health care pundits and faddists; its nutritional and biomedical attributes may be validated, anecdotal or fantasy. Vitamin E is a mixture of tocopherols (TPs) and tocotrienols (T-3s), each class having four substitutional isomers (α-, β-, γ-, δ-). Vitamin E analogues attain only low concentrations in most tissues, necessitating exacting invasive techniques for analytical research.

Pulmonary Deposition of Radionucleotide-Labeled Palivizumab: Proof-of-Concept Study.

Objective: Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very expensive and requires multiple intramuscular injections over the RSV season. Here we present proof-of-concept data using nebulized palivizumab delivery as a promising new approach for the prevention or treatment of severe RSV infections, documenting both aerosol characteristics and pulmonary deposition patterns in the lungs of lambs.

Phase I/II Trial of the Combination of Lutetium Prostate specific Membrane Antigen 617 and Idronoxil (NOX66) in Men with End-stage Metastatic Castration-resistant Prostate Cancer (LuPIN).

Background: Trials of lutetium prostate specific membrane antigen (PSMA) in men with metastatic castration-resistant prostate cancer (mCRPC) have demonstrated good safety and efficacy, but combination strategies may improve outcomes. Idronoxil is a synthetic flavonoid derivative with radiosensitising properties.

Objective: To evaluate the safety and activity of Lu PSMA 617 (LuPSMA-617) in combination with idronoxil suppositories (NOX66) in patients with end-stage mCRPC.

Enhancing the anti-tumour activity of Lu-DOTA-octreotate radionuclide therapy in somatostatin receptor-2 expressing tumour models by targeting PARP.

Peptide receptor radionuclide therapy (PRRT) is an important treatment option for patients with somatostatin receptor-2 (SSTR2)-expressing neuroendocrine tumour (NET) though tumour regression occurs in only a minority of patients. Therefore, novel PRRT regimens with improved therapeutic activity are needed. Radiation induced DNA damage repair is an attractive therapeutic target to increase PRRT efficacy and consequently, we have characterised a panel of preclinical models for their SSTR2 expression, in vivo growth properties and response to Lu-DOTA-octreotate (LuTate) PRRT to identify models with features suitable for evaluating novel therapeutic combinations.

Long-Term Follow-up and Outcomes of Retreatment in an Expanded 50-Patient Single-Center Phase II Prospective Trial of Lu-PSMA-617 Theranostics in Metastatic Castration-Resistant Prostate Cancer.

Lu-PSMA-617 is a radioligand with high affinity for prostate-specific membrane antigen (PSMA), enabling targeted β-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castration-resistant prostate cancer. We now report their longer-term outcomes, including a 20-patient extension cohort and outcomes of subsequent systemic treatments after completion of trial therapy.

Independent and incremental value of ventilation/perfusion PET/CT and CT pulmonary angiography for pulmonary embolism diagnosis: results of the PECAN pilot study.

Purpose: This pilot study assessed the independent and incremental value of Ga-V/Q PET/CT as compared with CT pulmonary angiography (CTPA) for the management of cancer patients with suspected acute pulmonary embolism (PE).

Methods: All 24 cancer patients with suspected acute PE prospectively recruited underwent both Ga-V/Q PET/CT and CTPA within 24 h. PET/CT was acquired after inhalation of Galligas prepared using a Technegas generator and administration of Ga-macroaggregated albumin.

Radiolabelled Aptamers for Theranostic Treatment of Cancer.

Cancer has a high incidence and mortality rate worldwide, which continues to grow as millions of people are diagnosed annually. Metastatic disease caused by cancer is largely responsible for the mortality rates, thus early detection of metastatic tumours can improve prognosis. However, a large number of patients will also present with micrometastasis tumours which are often missed, as conventional medical imaging modalities are unable to detect micrometastases due to the lack of specificity and sensitivity.

Results of a Prospective Phase 2 Pilot Trial of Lu-PSMA-617 Therapy for Metastatic Castration-Resistant Prostate Cancer Including Imaging Predictors of Treatment Response and Patterns of Progression.

Background: Lu-PSMA-617 (Lu-PSMA) is an emerging therapy in men with metastatic castration-resistant prostate cancer. Paired theranostic agents have the potential to visually identify phenotypes that will respond to targeted therapy. This study examined the value of Ga-HBEDD PSMA-11; prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in predicting treatment response and disease progression in Lu-PSMA therapy within the context of a phase 2 prospective pilot trial.

Dosimetry of Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: Correlations Between Pretherapeutic Imaging and Whole-Body Tumor Dosimetry with Treatment Outcomes.

Lu-prostate-specific membrane antigen (PSMA)-617 enables targeted delivery of β-particle radiation to prostate cancer. We determined its radiation dosimetry and relationships to pretherapeutic imaging and outcomes. Thirty patients with prostate cancer receiving Lu-PSMA-617 within a prospective clinical trial (ACTRN12615000912583) were studied.

[Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study.

Background: Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments.

A First-in-Human Study of Ga-Nanocolloid PET/CT Sentinel Lymph Node Imaging in Prostate Cancer Demonstrates Aberrant Lymphatic Drainage Pathways.

Our goal was to assess the feasibility, safety, and utility of a novel Ga-nanocolloid radiotracer with PET/CT lymphoscintigraphy for identification of sentinel lymph nodes (SLNs). This was a pilot study of patients from a tertiary cancer hospital who required insertion of gold fiducials for prostate cancer radiation therapy. Participation did not affect cancer management.

Cold Kit for Prostate-Specific Membrane Antigen (PSMA) PET Imaging: Phase 1 Study of Ga-Tris(Hydroxypyridinone)-PSMA PET/CT in Patients with Prostate Cancer.

Ga-labeled urea-based inhibitors of the prostate-specific membrane antigen (PSMA), such as Ga-labeled ,'-bis(2-hydroxybenzyl)ethylenediamine-,'-diacetic acid (HBED)-PSMA-11, are promising small molecules for targeting prostate cancer. A new radiopharmaceutical, Ga-labeled tris(hydroxypyridinone) (THP)-PSMA, has a simplified design for single-step kit-based radiolabeling. It features the THP ligand, which forms complexes with Ga rapidly at a low concentration, at room temperature, and over a wide pH range, enabling direct elution from a Ge/Ga generator into a lyophilized radiopharmaceutical kit in 1 step without manipulation.

High clinical and morphologic response using Y-DOTA-octreotate sequenced with Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours.

Purpose: Bulky disease is an adverse prognostic factor for Lu-DOTA-octreotate (Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). Y-DOTA-octreotate (Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially.

Gallium-68 perfusion positron emission tomography/computed tomography to assess pulmonary function in lung cancer patients undergoing surgery.

Background: Pre-operative evaluation of lung cancer patients relies on calculation of predicted post-operative (PPO) lung function based on split lung function testing. Pulmonary perfusion (Q) PET/CT can now be performed by substituting Technetium-99 m labeling of macroaggregated albumin (MAA) with Gallium-68. This study compares Q PET/CT with current recommended methods of pre-operative lung function assessment.

Correlation of 68Ga Ventilation-Perfusion PET/CT with Pulmonary Function Test Indices for Assessing Lung Function.

Unlabelled: Pulmonary function tests (PFTs) are routinely used to assess lung function, but they do not provide information about regional pulmonary dysfunction. We aimed to assess correlation of quantitative ventilation-perfusion (V/Q) PET/CT with PFT indices.

Methods: Thirty patients underwent V/Q PET/CT and PFT.

Initial Experience With Gallium-68 DOTA-Octreotate PET/CT and Peptide Receptor Radionuclide Therapy for Pediatric Patients With Refractory Metastatic Neuroblastoma.

Rationale: Pediatric patients with refractory neuroblastoma have limited therapeutic options. Neuroblastoma may express somatostatin receptors (SSTRs) allowing imaging with 68Ga-DOTA-Octreotate (GaTATE) positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT). We reviewed our experience with this theranostic combination.

68Ga-EDTA PET/CT imaging and plasma clearance for glomerular filtration rate quantification: comparison to conventional 51Cr-EDTA.

Unlabelled: Glomerular filtration rate (GFR) can accurately be determined using (51)Cr-ethylenediaminetetraacetic acid (EDTA) plasma clearance counting but is time-consuming and requires technical skills and equipment not always available in imaging departments. (68)Ga-EDTA can be readily available using an onsite generator, and PET/CT enables both imaging of renal function and accurate camera-based quantitation of clearance of activity from blood and its appearance in the urine. This study aimed to assess agreement between (68)Ga-EDTA GFR ((68)Ga-GFR) and (51)Cr-EDTA GFR ((51)Cr-GFR), using serial plasma sampling and PET imaging.

Favourable outcomes of (177)Lu-octreotate peptide receptor chemoradionuclide therapy in patients with FDG-avid neuroendocrine tumours.

Purpose: Increased glycolytic activity on FDG PET/CT defines a subgroup of patients with metastatic gastroenteropancreatic neuroendocrine tumour (NET) with a poor prognosis. A limited range of systemic treatment options exist for more aggressive NET. The role of peptide receptor chemoradionuclide therapy (PRCRT) in such patients is, however, unclear.