As interest in radiopharmaceutical therapies (RPT) dramatically grows, particularly in terms of a theranostics paradigm that combines diagnosis and therapy, there is major need for an individualized radiation dosimetry methodology tailored to the needs of RPT clinical trials. The aim of radiation dosimetry in RPT trials is to estimate the absorbed doses to healthy tissues (toxicity) and tumor lesions (efficacy) after administration of a therapeutic dose, and help identifying the optimal dose in Phase I trials.
Direct imaging of radionuclides and their decay chains at optimized time points enables the accurate quantification of the radiopharmaceutical’s time-dependent uptake, biodistribution and clearance. This facilitates the integration of measured time–activity data and computation of organ and lesion absorbed dose coefficients (i.e., absorbed doses per unit administered activity). With emerging alpha-emitting radiopharmaceuticals, direct imaging can be challenging and requires optimized imaging acquisition and reconstruction protocols to allow for good signal and counting statistics in an acceptable total scan duration for study participants. Surrogate radionuclides (positron- or single-photon- emitters) may also be used as an alternative way to estimate therapeutic absorbed doses, assuming similar pharmacokinetics and biodistribution in the theranostic pair.
Leading cro in radiation & Radiopharmaceutical therapy
Innovative Dosimetry Solutions by Medpace
Medpace, a leading CRO working in radiopharmaceuticals with over 30 years of experience in oncologic therapeutic development, is at the forefront of advancing these dosimetric approaches to meet your RPT trial needs. Medpace’s standardized and validated methods, focus on data quality and operational excellence to ensure reliable results in the required timeframe. From reviewing patient eligibility where analysis speed is critical, to monitoring safety limits for single patients to support ongoing treatment, or combined analyses of multiple patients for safety oversight and study endpoints, Medpace delivers.
Medpace imaging specialists and medical physicists support the creation of imaging protocols, guide the choice of imaging modalities, streamline schedules, and determine the sampling time points needed to optimize dosimetry calculations. Our dosimetry expert team will customize the dosimetry methodology for each study and provide solid estimates of biodistribution and radiation absorbed doses to tumor lesions and organs of interest.
When you partner with Medpace, your RPT program will benefit from:
Expert guidance on protocol, imaging acquisition, and analysis for dosimetry
Expertise with diagnostic, therapy, and theragnostics
Standardized workflow with rigorous documentation and manuals
Customizable data deliverables
Reviewing of clinical relevance by ABR certified radiation oncologists
“There has been a great focus in the nuclear medicine community on the personalization of dosimetry calculations in the last decades to establish evidence for a dose-response relationship, which is still a long run. But one other major aspect in clinical trials is to achieve the greatest consistency in dosimetry evaluations among study participants from various clinical centers, while limiting the patient burden. This starts with standardization or harmonization of applied imaging protocols and high-level data quality control, from scanners and instruments calibration to IP administration data, through organ contouring and lesion segmentation.
At Medpace, we have worked hard these past years to train the teams, streamline our processes, automatize all calculations even study-specific, and ensure full trackability, while matching the needs for tight turnaround times. This is a continual improvement process.”
Medpace Core Labs Offering for Quantitative Imaging and Dosimetry
Medpace Core Labs is dedicated to providing comprehensive services for quantitative imaging, radioactive PK and dosimetry, ensuring the highest standards in accuracy and quality. Services include:
Our experts are able to support the creation of the imaging protocol, guide the choice of imaging modalities, and determine the choice of sampling time points needed to optimize dosimetry calculations.
Isotope-specific verification of Dose Calibrator calibration
Cross-calibration of PET/CT scanners for absolute activity quantification (SUV)
SPECT/CT scanner for absolute activity quantification (biodistribution, dosimetry)
Gamma Counter calibration for local counting of radioactive biological samples
Medpace Core Labs utilizes a three-tiered approach to perform quality control procedures on all images received to confirm the data sets are correct, complete, and of adequate quality for study metrics to be obtained
Medpace Core Labs can also collect radioactive PK data from local gamma counting and perform quality control before PK data processing or analysis
Segmentation of regions of interest from PET/CT, SPECT/CT and planar whole-body scans
Uptake quantification in organs of interest and tumor lesions: Activity (Bq), Fraction of Administered Activity (%), Standardized Uptake Values (g/mL), Tumor-to-Background Ratios
Conversion of count rates (in counts per minute) from biological samples into activity concentrations (Bq/mL), for further non-compartmental PK analysis by Medpace Biostatistics.
Integration of Time-Activity Data, with Time Activity Curve (TAC) fitting in organs of interest and tumor lesions: estimation of the Time-Integrated Activity Coefficients (TIACs, formally known as “residence times”, in hrs)
Computation of Absorbed Doses (Gy) and Absorbed Dose Coefficients (mGy/MBq) to organs of interest and tumor lesions
Estimation of Whole-body Effective Dose (Sv), for diagnostic radiotracers
Estimation of Maximum Cumulative Activity (GBq) to administer over all therapy cycles, not to exceed existing dose limits to Organs At Risk (OAR)
Integrated Expertise in Dosimetry
Integrate dosimetry seamlessly into your study by combining the dosimetry expertise of Medpace Core Labs with the operational expertise of Medpace CRO study teams to manage your trial means complete efficiency in execution. With our integrated services and systems, we achieve higher levels of efficiency and productivity, from trial inception to completion.
Our Medical team, Clinical Trial Managers, dosimetry experts and imaging technologists evaluate the protocol holistically to streamline study schedules and imaging protocols, ensuring protocols are appropriate for patients and sites whilst meeting the study endpoints
Clinical operations, Data Management and Medpace Imaging Core Lab work in partnership to develop data capture systems which work in harmony, providing an optimal user experience for site staff and efficient, high quality data collection
Throughout the trial, CRAs work seamlessly with Medpace Imaging Core Lab imaging technologists to clean and verify data and provide ongoing site support
Truly cross-functional and comprehensive site training and support from beginning to end
