Biodistribution, Dosimetry, and Safety of 68Ga-EV203 in Hematological Malignancies

Zhejiang Cancer Hospital30 enrolled

Overview

The goal of this clinical trial is to evaluate the biodistribution, radiation dosimetry, safety, and time-dependent image quality of \^68\^Ga-EV203 injection in patients with hematological malignancies (multiple myeloma, non-Hodgkin lymphoma, or acute myeloid leukaemia), aged 18-75 years, who are able to lie still for 0.5 h and have no contraindications (e.g., pregnancy, recent radiotherapy, etc.). The main questions it aims to answer are: What are the biodistribution (organ uptake, %ID, SUV) and radiation absorbed doses (mGy/MBq) of \^68\^Ga-EV203 in target organs and the whole body? What is the safety profile of \^68\^Ga-EV203, as measured by adverse events and serious adverse events? How does the PET/CT image quality differ between the 30-, 60-, 90-, and 120-minute time points after injection? If there is a comparison group: Researchers will compare the positive percent agreement (PPA) and positive predictive value agreement (PPrA) of \^68\^Ga-EV203 PET/CT against \^18\^F-FDG PET/CT to see if the new tracer offers comparable or superior diagnostic performance in detecting CXCR4-positive lesions. Participants will: Receive a single intravenous injection of 74-296 MBq of \^68\^Ga-EV203. Undergo whole-body PET/CT scans at 30 min, 60 min, 90 min, and 120 min post-injection on the same day. Return within 3-7 days (but at least 2 days later) for a standard \^18\^F-FDG PET/CT scan after fasting for ≥5 h. Attend a safety follow-up visit at day 8-14 for physical examination, vital signs, and laboratory tests (blood count, coagulation, and biochemistry).

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Interventions

68Ga-EV203 PET/CTDIAGNOSTIC_TEST

This arm is distinguished by: (1) a novel CXCR4-targeting cyclic peptide, 68Ga-EV203, with \>10-fold higher binding affinity than the benchmark 68Ga-Pentixafor, enabling superior tumor-to-background contrast. (2) Four sequential whole-body PET/CT scans at 30, 60, 90, and 120 min post-injection to construct time-activity curves and compute organ-specific absorbed doses (mGy/MBq) and effective dose (mSv/MBq) using OLINDA/EXM-a formal dosimetry endpoint absent in routine diagnostic imaging. (3) Mandatory paired 18F-FDG PET/CT within 3-7 days for direct intrapatient head-to-head diagnostic comparison . (4) Strict enrollment limited to three defined hematological subtypes (MM, NHL, AML) per WHO 2022, with explicit washout periods (≥2 weeks from last anticancer therapy, ≥8 weeks from radiotherapy). (5) A 14-day safety follow-up including laboratory tests (CBC, coagulation, biochemistry) and rigorous contraception requirements for 3 months post-dose.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18 to 75 years (inclusive) at screening. * Able to lie still on the scanning bed for 0.5 hours. * Willing to sign informed consent and able to comply with protocol requirements. * Histologically/cytologically confirmed diagnosis of multiple myeloma (MM), non-Hodgkin lymphoma (NHL), or acute myeloid leukaemia (AML) according to the 2022 WHO Classification of Haematolymphoid Tumours. Exclusion Criteria: * Has claustrophobia or any other condition that prevents tolerance of imaging procedures * Has undergone major surgery within 3 months prior to screening, or plans to undergo surgery during the study period. * Has received any other radiopharmaceutical imaging agent or therapeutic radiopharmaceutical within 30 days prior to screening. * Is pregnant or lactating at screening. * Is a woman of childbearing potential or a man who does not agree to use effective contraception during the study (from signing informed consent) and for 3 months after study drug administration. * Has a known allergy to alcohol or any component of the investigational product, or has other allergies judged by the investigator to increase the participant's risk. * Has clinically significant cardiovascular disease within 6 months prior to screening (e.g., myocardial infarction, unstable angina, symptomatic congestive heart failure, uncontrolled severe arrhythmia). * Has uncontrolled hypertension, or a history of coagulopathy or coagulation disorders. * Has been diagnosed with another malignancy (other than the target haematological disease) within 5 years prior to 68Ga-EV203 administration. * Has received any systemic anti-cancer therapy within 2 weeks prior to planned 68Ga-EV203 administration, or radiotherapy within 8 weeks prior to planned administration. * Has any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in the study.

Outcomes

Primary Outcomes

Percentage of Injected Dose (%ID) and Standardized Uptake Values (SUVmean and SUVmax) in Target Organs Measured by PET/CT Imaging

Radioactivity concentration in major organs (including brain, lungs, heart, liver, spleen, kidneys, bladder, bone, and gastrointestinal tract) is quantified as percentage of injected dose (%ID) and mean/maximum standardized uptake values (SUVmean/SUVmax) using three-dimensional volumes of interest (VOIs). Data will be summarized using descriptive statistics (mean, standard deviation, median, minimum, and maximum) across all participants.

Time frame: Day 1 - PET/CT scans are acquired at 30 minutes (±5 minutes), 60 minutes (±10 minutes), 90 minutes (±10 minutes), and 120 minutes (±15 minutes) after intravenous injection of 68Ga-EV203.

Organ-Specific Radiation Absorbed Doses (mGy/MBq) and Whole-Body Effective Dose (mSv/MBq) Calculated via OLINDA/EXM Software

Time-activity curves (fitted with single- or bi-exponential models) are integrated to obtain cumulated activity for each organ. Absorbed doses (mGy/MBq) and whole-body effective dose (mSv/MBq) are computed using validated dosimetry software (OLINDA/EXM or MIRDcalc) with ICRP reference phantoms. Results will be reported as mean, standard deviation, and range across participants.

Number of Participants with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI-CTCAE Version 5.0

All adverse events and serious adverse events occurring from study drug administration through the final safety visit are recorded and graded for severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Data will be summarized as frequencies and percentages of participants experiencing each type and grade of event.

Time frame: Adverse event monitoring begins from the time of injection on Day 1 and continues through the safety follow-up visit, which occurs between Day 8 and Day 14 post-injection.

Secondary Outcomes

Tumor-to-Background Ratios (TBR) Derived from PET/CT Images at Four Consecutive Post-Injection Time Points

Tumor-to-background ratios (lesion SUVmax divided by liver SUVmean and by blood-pool SUVmean) are calculated at 30, 60, 90, and 120 minutes after injection to evaluate time-dependent image quality. Differences across time points will be summarized using paired descriptive statistics (means and standard deviations).