Related Experiment Video
Updated: Sep 28, 2026
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
The development of [(124)I]iodinated-VG76e: a novel tracer for imaging vascular endothelial growth factor in vivo
David R Collingridge1, Veronica A Carroll, Mathias Glaser
1Cancer Research UK Positron Emission Tomography Oncology Group, Department of Cancer Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London W12 0NN.
Abstract:
The development of anticancer therapies that target the angiogenic process is an area of major growth in oncology. A method of noninvasively measuring tumor vascular endothelial growth factor (VEGF) in vivo could provide important efficacy information for VEGF-dependent antiangiogenic agents and the role of VEGF in cancer biology. We have developed a novel radiotracer for use with positron emission tomography (PET) that enables noninvasive imaging of VEGF. This radiotracer comprises an IgG1 monoclonal antibody, known as VG76e, that binds to human VEGF, labeled with a positron-emitting radionuclide, iodine-124 ([(124)I]-SHPP-VG76e). Three radiolabeling strategies were evaluated to synthesize the radiotracer with optimal radiochemical yield, purity, and immunoreactivity. To evaluate the pharmacokinetics and VEGF-specific localization of [(124)I]-SHPP-VG76e, two subclones of the HT1080 human fibrosarcoma selected on the basis of differing VEGF production (26.6 and 1/3C, the former producing 2-4-fold more in vitro) were established in culture and grown as solid tumor xenografts in immune-deficient mice. A single i.v. injection of the radiotracer into tumor-bearing mice revealed a time dependent and specific localization of [(125)I]-SHPP-VG76e to the tumor tissue. Three validation studies established the VEGF specificity and potential for use of [(124)I]-SHPP-VG76e in vivo: (a) uptake of [(125)I]-SHPP-VG76e was 1.8-fold higher in HT1080-26.6 compared with HT1080-1/3C tumors (P < 0.05); (b) uptake of [(125)I]-SHPP-VG76e in HT1080-26.6 tumors was specifically blocked by prior administration of excess unlabeled VG76e (P < 0.05); and (c) tumor uptake of the IgG1, [(125)I]-SHPP-CIP5, which has a similar molecular weight as [(125)I]-SHPP-VG76e but does not recognize VEGF, was the same for both HT1080-26.6 and HT1080-1/3C (P > 0.05). Other than tumor localization, [(125)I]-SHPP-VG76e was present in urine and blood and to a lesser extent in heart, lungs, liver, kidney, and spleen. Whole-animal PET imaging studies revealed a high tumor-to-background contrast and also revealed [(124)I]-SHPP-VG76e distributions in the major organs. These studies support further development of [(124)I]-SHPP-VG76e as a radiotracer for measuring tumor levels of VEGF in humans.
Insights
A novel positron emission tomography (PET) radiotracer, [(124)I]-SHPP-VG76e, enables noninvasive imaging of vascular endothelial growth factor (VEGF) in tumors. This tracer shows specific tumor uptake and holds promise for monitoring anti-angiogenic therapies.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Targeting tumor angiogenesis is a key strategy in cancer therapy.
- Noninvasive methods to measure tumor vascular endothelial growth factor (VEGF) are crucial for evaluating anti-angiogenic agents.
- VEGF plays a significant role in cancer biology and progression.
Purpose of the Study:
- To develop a novel radiotracer for noninvasive positron emission tomography (PET) imaging of VEGF in vivo.
- To evaluate the pharmacokinetic properties and tumor-specific localization of the developed radiotracer, [(124)I]-SHPP-VG76e.
- To validate the VEGF-specificity and potential clinical utility of [(124)I]-SHPP-VG76e for assessing tumor VEGF levels.
Main Methods:
- Synthesis and optimization of the radiotracer [(124)I]-SHPP-VG76e, an IgG1 monoclonal antibody (VG76e) targeting human VEGF, labeled with iodine-124.
- Pharmacokinetic and biodistribution studies in HT1080 human fibrosarcoma xenografts with differing VEGF production in immune-deficient mice.
- Validation studies including comparative tumor uptake, blocking studies with unlabeled VG76e, and control antibody studies.
Main Results:
- [(124)I]-SHPP-VG76e demonstrated time-dependent and specific localization to tumor tissue.
- Tumors with higher VEGF production showed significantly higher uptake of the radiotracer.
- Blocking studies confirmed the specific binding of [(124)I]-SHPP-VG76e to VEGF, and control antibody studies showed no specific tumor targeting.
- Whole-animal PET imaging revealed high tumor-to-background contrast and distribution in major organs.
Conclusions:
- [(124)I]-SHPP-VG76e is a promising novel radiotracer for noninvasive in vivo imaging of VEGF.
- The developed PET imaging agent allows for specific measurement of tumor VEGF levels.
- Further development of [(124)I]-SHPP-VG76e is supported for clinical application in monitoring anti-angiogenic therapies and understanding VEGF's role in cancer.
Related Concept Videos
01:29Positron Emission Tomography
One of the main requirements of a PET scan is a positron-emitting radioisotope, which is produced in a cyclotron and then attached to a substance used by the part of the body being...
01:25Imaging Studies II: Positron Emission Tomography and Scintigraphy
Fundamental Principles of PET