The radiopharmaceutical industry has traditionally experienced steady but modest growth, primarily driven by its established role in diagnostics and nuclear imaging across clinical medicine. However, in recent years, the landscape has undergone a marked transformation. Recent technological advances – particularly in isotope production such as Actinium-225 (Ac-225) – are unlocking new therapeutic applications and expanding the clinical potential of radiopharmaceuticals beyond imaging into targeted radiotherapy. At the same time, increasing investment from pharmaceutical companies, coupled with strategic collaborations between pharma, academic research institutions, and CROs, is accelerating innovation and reducing development timelines.
How radiopharmaceuticals work
Targeted radiopharmaceuticals typically comprise four key components: a targeting molecule (such as an antibody), a linker, a chelating agent, and a radionuclide. Conceptually similar to antibody-drug conjugates (ADCs), these agents aim to replace non-specific external beam or systemic radiotherapy by offering a more selective approach. The targeting molecule directs the radiopharmaceutical through the body to specific tissues or organs, where it accumulates in the tumour microenvironment. Once localised, the radionuclide either emits radiation for imaging purposes or delivers high-energy radiation that destroys or significantly damages malignant cells, while minimising exposure and toxicity to surrounding healthy tissues.
Therapeutic Applications
Targeted radiotherapeutics have gained significant momentum, particularly in prostate cancer and neuroendocrine tumours, driven by a relatively high number of actionable molecular targets, substantial unmet clinical needs, and the inherent radiosensitivity of these malignancies. Emerging developments are also being explored in other indications, such as breast and lung cancer, where targeted approaches are beginning to show promise. In parallel, the integration of diagnostics and therapeutics – known as theranostics, is advancing personalised treatment strategies. By leveraging specific diagnostic imaging biomarkers, theranostics enables precise patient selection and the customisation of treatment protocols, ultimately improving patient outcomes and enhancing the overall efficiency of care.
PK, immunogenicity and biomarker analysis – best approaches
Growing regulatory requirements, particularly concerning the handling of radioactive materials, radiation safety, and environmental compliance are driving the need for greater expertise throughout the radiopharmaceutical development process. We’ve encountered an increasing demand for specialised services, particularly in managing radioactive specimens, conducting integrated theranostic trials, advancing imaging studies, and navigating complex regulatory frameworks.
There are three core bioanalytical approaches for radiopharmaceuticals:
PK Analysis
Ligand binding assays are commonly used during nonclinical and clinical pharmacokinetic studies to quantify drug concentrations in biological matrices such as plasma, serum, or tissue homogenates. Platforms include sandwich immunoassays, target-capture assays, total and free antibody-drug conjugate (ADC) assays, target-bridging assays, and anti-idiotype (anti-ID) bridging assays. Synexa also supports the measurement of total radioactivity in study samples. These assays enable precise quantification of the therapeutic agent over time, supporting critical evaluations of absorption, distribution, metabolism, and elimination (ADME) profiles necessary for dose optimisation and regulatory submissions.
Immunogenicity
Immunogenicity testing is conducted during all phases of drug development, especially at key regulatory milestones, to monitor immune responses to the therapeutic. Ligand binding assays (e.g., bridging or direct formats including acid dissociation protocols), competitive receptor binding assays and cell-based assays are employed for initial screening, confirmation, cross-reactivity assessment, and the characterisation of neutralising antibodies (NAbs). Detecting and characterising anti-drug antibodies (ADAs) is essential to understanding potential impacts on safety, efficacy, and pharmacokinetics, and is a regulatory requirement for biologic therapies.
Biomarkers
Biomarker analysis is performed on “hot samples” (radioactive specimens) throughout the clinical development process, often alongside PK and immunogenicity studies. Techniques such as MSD (Meso Scale Discovery), ELISA, Gyrolab, RIA, Delfia and LC-MS/MS are used depending on assay sensitivity needs, throughput, and sample volume constraints. Biomarkers provide critical insights into the mechanism of action, pharmacodynamic responses, patient stratification, and treatment efficacy, enhancing clinical decision-making and supporting regulatory filings.
Safety
Safety will always be paramount in the development and analysis of radiopharmaceuticals. Given the inherently radioactive nature of these products, CROs must continuously advance their safety management protocols, invest in rigorous staff training, and ensure full compliance with radiation protection standards. Enhanced monitoring and comprehensive risk assessment processes are essential to safeguard patients, research personnel, and the environment. As regulatory guidelines continue to evolve, particularly around radiopharmaceutical safety, isotope handling, and radioactive waste management, CROs must remain vigilant and proactive in meeting these requirements. Although many radiopharmaceuticals have relatively short half-lives, thereby reducing overall radiation exposure over time, meticulous handling and strict adherence to safety protocols remain critical.
About Synexa Life Sciences
At Synexa Life Sciences, we offer PK, immunogenicity and biomarker analysis for radioactive study samples, including when a license is needed for work with radioactive samples above the free limits, known as “hot samples”. Additionally, quantification of sample radioactivity, radioimmunoassay method development/validation as well as preclinical (GLP) and clinical (GCLP) sample analyses are supported. Adhering strictly to regulatory standards for safety and efficacy, our team is licensed and experienced in handling a variety of key isotopes, including H-3, In-111, I-125, I-131, Ac-225 and Th-227. We can also work with a wide range of other radioactive substances with expedited approval to meet the sponsor’s needs.
For more information on specialised services for radiopharmaceutical drug development, reach out to us at contactus@synexagroup.com.
