An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab.

Background: Atezolizumab is a programmed death-ligand 1 (PD-L1) checkpoint inhibitor for the treatment of different forms of cancer. The subcutaneous formulation of atezolizumab has recently received approval. However, treatment with atezolizumab continues to be expensive, and the number of patients needing treatment with this drug continues to increase.

A Multiradionuclide Automatic Dispensing System for Syringes of Radiopharmaceuticals: The Effect on Operator Hand Dose.

The radiation exposure of the hands of nuclear medicine laboratory technicians is largely due to the dispensing of radiopharmaceuticals into syringes. To reduce this exposure, a multiradionuclide automatic dispensing system (ADS) for syringes of radiopharmaceuticals was introduced. The aim of this study was to determine the effect of this ADS on hand dose compared with manual dispensing.

Model-Informed Development of a Cost-Saving Dosing Regimen for Sacituzumab Govitecan.

Background: The antibody-drug conjugate sacituzumab govitecan is approved for metastatic triple-negative breast cancer and has shown promising results in various other types of cancer. Its costs may limit patient access to this novel effective treatment modality.

Objective: The purpose of this study was to develop an evidence-based rational dosing regimen that results in targeted drug exposure within the therapeutic range while minimizing financial toxicity, to improve treatment access.

Quantification of biochemical PSA dynamics after radioligand therapy with [Lu]Lu-PSMA-I&T using a population pharmacokinetic/pharmacodynamic model.

Background: There is an unmet need for prediction of treatment outcome or patient selection for [Lu]Lu-PSMA therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Quantification of the tumor exposure-response relationship is pivotal for further treatment optimization. Therefore, a population pharmacokinetic (PK) model was developed for [Lu]Lu-PSMA-I&T using SPECT/CT data and, subsequently, related to prostate-specific antigen (PSA) dynamics after therapy in patients with mCRPC using a pharmacokinetic/pharmacodynamic (PKPD) modelling approach.

Automated radiolabelling of [Ga]Ga-PSMA-11 (gallium (Ga)-gozetotide) using the Locametz® kit and two generators.

Background: Steps have been taken by pharmaceutical companies to obtain marketing authorisation of PSMA ligands in the European Union. Since December 2022, Locametz® (PSMA-11, gozetotide) is licensed as kit for manual radiolabelling with gallium-68 and commercially available since mid-2023. The Summary of Product Characteristic (SmPC) describes manual radiolabelling with a maximum activity after radiolabelling of 1369 MBq.

Extravasation After [ 177 Lu]Lu-HA-DOTATATE Therapy.

Extravasation of the radiopharmaceutical during peptide receptor radionuclide therapy infusion is an unwanted infrequently reported event. We present the case of a 74-year old woman with a neuroendocrine tumor who was referred for peptide receptor radionuclide therapy. During intravenous infusion of 7.

TcPSMA-radioguided surgery in oligorecurrent prostate cancer: the randomised TRACE-II trial.

Objective: To investigate whether combination treatment of prostate-specific membrane antigen (PSMA)-based radioguided surgery (RGS) with short-term androgen deprivation therapy (ADT) improves oncological outcomes in men with oligorecurrent prostate cancer (PCa) as compared to treatment with short-term ADT only.

Methods: The TRACE-II study is an investigator-initiated, prospective, randomised controlled clinical trial. Patients (aged >18 years) with hormone-sensitive recurrent PCa after radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy), with involvement of ≤2 lymph nodes or local oligorecurrent disease within the pelvis as determined by PSMA positron emission tomography (PET)/computed tomography (CT) are randomly assigned in a 1:1 ratio between 6-month ADT (Arm A) or 6-month ADT plus RGS (Arm B).

Validation of an automated dispensing system for subsequent dose dispensing of different radionuclides.

Background: Automated dispensing systems (ADSs) for radiopharmaceuticals have been developed to reduce the radiation exposure of personnel, to improve the accuracy of the dispensed dose and to limit the microbiological contamination. However, before implementing such systems, validation according to various applicable guidelines is necessary to ensure safety and quality. Here we present the selection, validation and implementation of the PT459R2 from manufacturer Lynax s.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development.

Main Body: This selection of highlights provides commentary on 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals.

Conclusion: Trends in radiochemistry and radiopharmacy are highlighted.

The cycle effect quantified: reduced tumour uptake in subsequent cycles of [Lu]Lu-HA-DOTATATE during peptide receptor radionuclide therapy.

Background: Clear evidence regarding the effect of reduced tumour accumulation in later peptide receptor radionuclide therapy (PRRT) cycles is lacking. Therefore, we aimed to quantify potential cycle effects for patients treated with [Lu]Lu-HA-DOTATATE using a population pharmacokinetic (PK) modelling approach.

Methods: A population PK model was developed using imaging data from 48 patients who received multiple cycles of [Lu]Lu-HA-DOTATATE.

Predicting [Lu]Lu-HA-DOTATATE kidney and tumor accumulation based on [Ga]Ga-HA-DOTATATE diagnostic imaging using semi-physiological population pharmacokinetic modeling.

Background: Prediction of [Lu]Lu-HA-DOTATATE kidney and tumor uptake based on diagnostic [Ga]Ga-HA-DOTATATE imaging would be a crucial step for precision dosing of [Lu]Lu-HA-DOTATATE. In this study, the population pharmacokinetic (PK) differences between [Lu]Lu-HA-DOTATATE and [Ga]Ga-HA-DOTATATE were assessed and subsequently [Lu]Lu-HA-DOTATATE was predicted based on [Ga]Ga-HA-DOTATATE imaging.

Methods: A semi-physiological nonlinear mixed-effects model was developed for [Ga]Ga-HA-DOTATATE and [Lu]Lu-HA-DOTATATE, including six compartments (representing blood, spleen, kidney, tumor lesions, other somatostatin receptor expressing organs and a lumped rest compartment).

Predicting the effect of different folate doses on [Ga]Ga-PSMA-11 organ and tumor uptake using physiologically based pharmacokinetic modeling.

Background: Folate intake might reduce [Ga]Ga-PSMA-11 uptake in tissues due to a competitive binding to the PSMA receptor. For diagnostic imaging, this could impact decision making, while during radioligand therapy this could affect treatment efficacy. The relationship between folate dose, timing of dosing and tumor and organ uptake is not well established.

Redispensing of expensive oral anticancer medicines: A practical application.

Introduction: Increasing use of expensive oral anticancer medicines comes with the downside of a financial and environmental burden, partially caused by unused medication. Returned oral anticancer medicine to the pharmacy could be considered for redispensing providing guaranteed quality. This study aimed to identify and implement quality aspects and criteria for redispensing oral anticancer medicine in daily pharmacy practice.

A Systematic Evaluation of Cost-Saving Dosing Regimens for Therapeutic Antibodies and Antibody-Drug Conjugates for the Treatment of Lung Cancer.

Background: Expensive novel anticancer drugs put a serious strain on healthcare budgets, and the associated drug expenses limit access to life-saving treatments worldwide.

Objective: We aimed to develop alternative dosing regimens to reduce drug expenses.

Methods: We developed alternative dosing regimens for the following monoclonal antibodies used for the treatment of lung cancer: amivantamab, atezolizumab, bevacizumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and ramucirumab; and for the antibody-drug conjugate trastuzumab deruxtecan.

Tolerability of concurrent external beam radiotherapy and [Lu]Lu-PSMA-617 for node-positive prostate cancer in treatment naïve patients, phase I study (PROQURE-I trial).

Background: Prostate cancer patients with locoregional lymph node disease at diagnosis (N1M0) still have a limited prognosis despite the improvements provided by aggressive curative intent multimodal locoregional external beam radiation therapy (EBRT) with systemic androgen deprivation therapy (ADT). Although some patients can be cured and the majority of patients have a long survival, the 5-year biochemical failure rate is currently 29-47%. [Lu]Lu-PSMA-617 has shown impressive clinical and biochemical responses with low toxicity in salvage setting in metastatic castration-resistant prostate cancer.

Predicting outcomes in chronic kidney disease: needs and preferences of patients and nephrologists.

Introduction: Guidelines on chronic kidney disease (CKD) recommend that nephrologists use clinical prediction models (CPMs). However, the actual use of CPMs seems limited in clinical practice. We conducted a national survey study to evaluate: 1) to what extent CPMs are used in Dutch CKD practice, 2) patients' and nephrologists' needs and preferences regarding predictions in CKD, and 3) determinants that may affect the adoption of CPMs in clinical practice.

A physiologically based pharmacokinetic model for [Ga]Ga-(HA-)DOTATATE to predict whole-body distribution and tumor sink effects in GEP-NET patients.

Background: Little is known about parameters that have a relevant impact on (dis)similarities in biodistribution between various Ga-labeled somatostatin analogues. Additionally, the effect of tumor burden on organ uptake remains unclear. Therefore, the aim of this study was to describe and compare organ and tumor distribution of [Ga]Ga-DOTATATE and [Ga]Ga-HA-DOTATATE using a physiologically based pharmacokinetic (PBPK) model and to identify factors that might cause biodistribution and tumor uptake differences between both peptides.

Somatostatin receptor saturation after administration of high peptide amounts of [Lu]Lu-HA-DOTATATE: when enough is enough.

Background: Receptor saturation during peptide receptor radionuclide therapy (PRRT) could result in altered [Lu]Lu-HA-DOTATATE uptake in tumors and organs. Therefore, receptor expression status and effects of different (unlabeled) administered peptide amounts during PRRT need to be evaluated. The aim of this study was to assess potential receptor saturation during PRRT by comparing organ and tumor uptake after administration of [Lu]Lu-HA-DOTATATE with low, standard and high administered peptide amounts in patients with advanced metastatic neuroendocrine tumors (NETs).

Alternative dosing strategies for immune checkpoint inhibitors to improve cost-effectiveness: a special focus on nivolumab and pembrolizumab.

Immune checkpoint inhibitors have revolutionised cancer treatment by offering durable responses to many patients with solid and haematological cancers. The high prices and increasing use of immune checkpoint inhibitors put considerable strain on health-care budgets globally. This financial strain could jeopardise patients' access to these anti-cancer therapies.

Radiolabeling and quality control of therapeutic radiopharmaceuticals: optimization, clinical implementation and comparison of radio-TLC/HPLC analysis, demonstrated by [Lu]Lu-PSMA.

Background: Radiopharmaceuticals are considered as regular medicinal products and therefore the same regulations as for non-radioactive medicinal products apply. However, specific aspects should be considered due to the radiochemical properties. Radiopharmaceutical dedicated monographs are developed in the European Pharmacopoeia to address this.

Improving Appropriate Prescribing For Geriatric Patients Using a Clinical Decision Support System.

Polypharmacy is a known risk factor for potentially inappropriate prescribing. Recently there is an increasing interest in clinical decision support systems (CDSS) to improve prescribing. The objective of this study was to evaluate the impact of a CDSS, with the START-STOPP criteria as main content in the setting of a geriatric ward.