177 Lu-PSMA With Olaparib Radiosensitization Potentiates Response and Toxicity in Extensive Castration-Resistant Metastatic Prostate cancer.

A patient with widespread intensely prostate-specific membrane antigen-expressing, BRCA gene mutation-positive bone metastases at the time of prostate cancer diagnosis had progressed on multiple lines of standard therapy. He received 177 Lu-prostate-specific membrane antigen 8.5 GBq augmented by a short course of olaparib radiosensitization and achieved 90% decrease in serum PSA level after a single treatment.

First-Strike Rapid Predictive Dosimetry and Dose Response for Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer.

We devised and clinically validated a schema of rapid personalized predictive dosimetry for Lu-PSMA-I&T in metastatic castration-resistant prostate cancer. It supersedes traditional empiric prescription by providing clinically meaningful predicted absorbed doses for first-strike optimization. Prostate-specific membrane antigen PET was conceptualized as a simulation study that captures the complex dosimetric interplay between tumor, marrow, and kidneys at a single time point.

Rapid predictive dosimetry for radioembolization.

Economics of today's busy clinical practice demand both time and cost-efficient methods of predictive dosimetry for liver radioembolisation. A rapid predictive schema adapted from the Medical Internal Radiation Dose (MIRD) method i.e.

A simplified general schema for rapid single time-point marrow predictive dosimetry.

The red marrow is often the dose-limiting organ in systemic radionuclide therapy. However, multi-time-point personalised predictive dosimetry is resource intensive and impractical for routine clinical implementation. Single-time-point methods are a reasonable alternative for streamlining dosimetric workflows.

First Strike personalized predictive radioiodine prescription for inoperable metastatic differentiated thyroid cancer.

Objectives: The traditional practice of empiric radioiodine (I-131) prescription is scientifically obsolete and inappropriate for inoperable metastatic differentiated thyroid cancer. However, theranostically guided prescription is still years away for many institutions. A personalized predictive method of radioiodine prescription that bridges the gap between empiric and theranostic methods is presented.

Empiric radioiodine for hyperthyroidism: Outcomes, prescribing patterns, and its place in the modern era of theranostics.

Background: The modern era of radioiodine (I-131) theranostics for metastatic differentiated thyroid cancer requires us to rationalize the role of traditional empiric prescription in nonmalignant thyroid disease. We currently practice empiric I-131 prescription for treatment of hyperthyroidism. This study aims to assess outcomes after treatment of hyperthyroidism by empiric I-131 prescription at our centre, evaluate factors that impact on outcomes and prescribing practice, and gain insight into whether there is a place for theranostically-guided prescription in hyperthyroidism.

Indirect Lung Absorbed Dose Verification by Y PET/CT and Complete Lung Protection by Hepatic Vein Balloon Occlusion: Proof of Concept.

Postradioembolization lung absorbed dose verification was historically problematic and impractical in clinical practice. We devised an indirect method using Y PET/CT. Conceptually, true lung activity is simply the difference between the total prepared activity minus all activity below the diaphragm and residual activity within delivery apparatus.

Brain hypometabolism in rare genetic neurodegenerative disease: Niemann-Pick disease type C, spinocerebellar ataxia and Huntington disease assessed by FDG PET.

Brain metabolic imaging using F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) with contemporaneous low-dose CT may be used to assess neurodegenerative diseases. In contrast to oncology whole-body FDG PET, qualitative assessment alone in brain FDG PET is subjective and vulnerable to visual interference due to high physiologic background activity. Therefore, mild changes in brain metabolism may be visually undetectable by qualitative interpretation alone, resulting in diagnostic inaccuracy.

Brain hypometabolic changes in 14 adolescent-adult patients with Niemann-Pick disease type C assessed by 18F-fluorodeoxyglucose positron emission tomography.

Objective: Niemann Pick disease type C (NPC) is a rare progressive neurovisceral lysosomal disorder caused by autosomal recessive mutations in the NPC1 or NPC2 genes. 18F-fluorodeoxyglucose (FDG) is a positron-emitting glucose analogue for non-invasive imaging of brain metabolism. FDG PET is commonly used for dementia imaging but its specific application to NPC is rarely described.

Light-Induced Histidine Adducts to an IgG1 Molecule Via Oxidized Histidine Residue and the Potential Impact of Polysorbate-20 Concentration.

Purpose: Histidine (His) undergoes light-induced reactions such as oxidation, crosslinking and addition. These reactions are initiated by singlet oxygen (O) to generate His photo-oxidation products, which are subject to nucleophilic attack by a non-oxidized His residue from another protein or by nucleophilic buffer components such as Tris and His. This report aims to identify light-induced His-adducts to a monoclonal antibody (mAb-1) due to the reaction of His molecules in the buffer with the photooxidized His residues under ICH light conditions.

Y PET for Qualitative and Quantitative Assessment of Residual Activity in Delivery Apparatus After Radioembolization.

Assessment of residual activity is critical for quality assurance after Y radioembolization. The resin microsphere manufacturer's indirect method of estimating the residual activity is laborious and vulnerable to inaccuracies. Furthermore, the method cannot localize the exact site of residual activity.

Dose-response for yttrium-90 resin microsphere radioembolisation.

The fundamental premise of yttrium-90 radioembolisation is to balance safety with efficacy. To achieve this, dose-response guidance must be provided. This is a tabulation of published data of key dose-response metrics for yttrium-90 resin microsphere radioembolisation of liver malignancies.

Probing the Impact of the Knob-into-Hole Mutations on the Structure and Function of a Therapeutic Antibody.

Bispecific antibodies (BsAbs) have drawn increasing interest in the biopharmaceutical industry due to their advantage to bind two distinct antigens simultaneously. The knob-into-hole approach is an effective way to produce bispecific antibodies by driving heterodimerization with mutations in the CH3 domain of each half antibody. To better understand the conformational impact by the knob and hole mutations, we combined size-exclusion chromatography (SEC), differential scanning calorimetry (DSC), and hydrogen-deuterium exchange mass spectrometry (H/D exchange MS), to characterize the global and peptide-level conformational changes.

Light-Induced Covalent Buffer Adducts to Histidine in a Model Protein.

Purpose: Light is known to induce histidine (His) oxidation and His-His crosslinking in proteins. The crosslinking is resulted from the nucleophilic attack of a His to a photooxidized His from another protein. The goal of this work is to understand if covalent buffer adducts on His residues can be generated by light through similar mechanisms in nucleophilic buffers such as Tris and His.

Recommendations for radioembolisation after liver surgery using yttrium-90 resin microspheres based on a survey of an international expert panel.

Introduction: Guidelines on how to adjust activity in patients with a history of liver surgery who are undergoing yttrium-90 radioembolisation (Y-RE) are lacking. The aim was to study the variability in activity prescription in these patients, between centres with extensive experience using resin microspheres Y-RE, and to draw recommendations on activity prescription based on an expert consensus.

Methods: The variability in activity prescription between centres was investigated by a survey of international experts in the field of Y-RE.

Structure-Based Correlation of Light-Induced Histidine Reactivity in A Model Protein.

Light is known to induce covalently linked aggregates in proteins. These aggregates can be immunogenic and are of concern for drug product development in the biotechnology industry. Histidine (His) is proposed to be a key residue in cross-link generation ( Pattison , D.

Yttrium-90 hepatic radioembolization: clinical review and current techniques in interventional radiology and personalized dosimetry.

In recent years, yttrium-90 ((90)Y) microsphere radioembolization has been establishing itself as a safe and efficacious treatment for both primary and metastatic liver cancers. This extends to both first-line therapies as well as in the salvage setting. In addition, radioembolization appears efficacious for patients with portal vein thrombosis, which is currently a contraindication for surgery, transplantation and transarterial chemoembolization.

Gender, Race, and Age at Diagnosis as Risk Factors for Metastasis or Recurrence among 1,657 Thyroid Cancer Patients Treated with Radioiodine across 40 Years in Singapore.

Background: To obtain descriptive data on Singaporean thyroid cancer patients treated with radioiodine and to assess gender, race, and age at diagnosis as risk factors for metastasis or recurrence.

Methods: This is a retrospective study of all thyroid cancer patients treated with radioiodine of any prescribed activity at our institution. Data collected included: age at diagnosis, gender, race, histopathological type, duration of follow-up, and metastasis at diagnosis (locoregional or distant) or recurrence at any time.

Scientific basis of personalised tomographic radiation planning for radioembolisation: A form of brachytherapy planning.

Today's tomographic imaging techniques such as catheter-directed CT and single photon emission computed tomography with integrated computed tomography may be used for pre-therapy radiation planning for radioembolisation based on prospective calculation of tissue radiation absorbed doses. We outline the scientific concepts that underlie modern personalised tomographic radiation planning for radioembolisation and highlight its similarities to brachytherapy planning.