Image of Ling-Jian Meng.

Urbana, Ill. Radiopharmaceutical therapy is an emerging type of radiation therapy with great potential for patients with metastatic cancer, who have diminished prospects for long-term survival.

This treatment uses alpha-particles (α-particles), such as Ac-225 and Ra-223, which cause highly disruptive and largely irreparable DNA double-strand breaks capable of killing a cell with as few as one to two tracks through the nucleus. Since α-particles travel a short distance (10-50 microns), this damage is confined to the vicinity of targeted cells or cell clusters, sparing more healthy tissue.

In clinical and preclinical studies, α-radiopharmaceutical therapies (α-RPTs) have been highly effective against metastasized cancer.

Ling-Jian Meng, Cancer Center at Illinois (CCIL) scientist and professor of nuclear, plasma, and radiological engineering (NPRE), recently received a $3.8M BRP/U01 and $2.5M R01 from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) in support of his research developing radiopharmaceutical therapy and a complementary molecular imaging modality.

Throughout the past 15 years, Meng’s career goals have always been pushing the sensitivity and spatial resolution of radiological imaging technologies to enable fellow scientists to acquire better data and images in deep tissue under clinical settings. Now, Meng applies the most advanced semiconductor radiation imaging sensors and a synthetic compound eye camera design, developed through several previous and ongoing projects focusing on imaging cancer, cardiovascular, and brain disorders, to advance the treatment of metastatic cancers, where α-RPT has been shown to be a promising approach.

To visualize the delivery and efficacy of α-RPT, Meng is collaborating with researchers and physicians at Johns Hopkins University School of Medicine to develop a hyperspectral single-photon imaging technique. The R01 grant is funding the development of pre-clinical multicolor, multispectral imaging of small animals, and the U01 supports translation of the technology to clinical use for patients.

In α-RPTs , tiny amounts of alpha particles are directly delivered to cancer cells at a very close range. These alpha particles are highly energetic and deposit a tremendous density of energy as they travel through tissue, enabling them to kill cancer cells. As these α-RPTs decay, they generate a long chain of other alpha-emitting daughter isotopes, which have different pharmacokinetics than the primary α-isotopes and can be distributed into different tissues and organs at different rates.

“It is critically important that we know the distribution of both the primary alpha isotope and its daughters since they have dramatic radio-toxicity to living tissues and limit the dose that can be administrated in patients,” Meng said. “The hyperspectral single-photon imaging system that will be developed under this recently started project could potentially distinguish and simultaneously visualize those alpha emitters – both the primary and the daughters – so we can know where they are going, how long it takes to deliver into cancer cells, and how long they take to wash out.”

Meng’s project aims to develop clinical single-photon emission computed tomography (SPECT) cameras using gamma-ray imaging sensors of unprecedented spectral resolution and sensitivity, which could effectively differentiate any combinations of medical radioisotopes currently in use in clinical diagnostic and therapeutic applications. This system would allow users to obtain simultaneous multi-color images to reveal several molecular processes that are occurring in the target region.

While the principle of multiple isotope imaging has long been established, the majority of molecular imaging practices using current positron emission tomography (PET) and SPECT are typically focused on monochromatic, single-function imaging of elements like blood flow.

“Since cancer involves the interplay of many molecular processes, there is a clear gap in existing clinical imaging capability at hand which limits our ability to study how cancer evolves and responds to therapy,” Meng said. “Through these recent awards, we hope to develop a new class of clinical SPECT systems that could produce multi-color, multifunctional images with significantly improved sensitivity and spatial resolution.”

The ability to image cellular and molecular processes, and their interplay, at the same time presents a significant technological advance and would enable a wide range of novel molecular imaging studies under clinical settings. So far, RPT has shown success in treating adult leukemia, glioblastoma multiforme, and hormone-refractory metastatic prostate cancer.

“Nuclear medicine has long been a powerful modality for clinical cancer research and treatment. I hope our research could help to transform the way that nuclear medicine is used in the diagnosis and treatment of a wide variety of diseases, such as cancer, cardiovascular diseases, and brain disorders,” Meng said.


– Written by the CCIL Communications Team

Ling-Jian Meng was awarded a $3.8M Biomedical Research Partnership (BRP/U01 grant) from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), titled “High Energy and Spatial Resolution Multi-Isotope SPECT imaging of Targeted Alpha-Emitters and their Daughters.” This project will be carried out by a large interdisciplinary research team led by Meng and George Sgouros from Johns Hopkins University School of Medicine.

Meng was also awarded a $2.5M research grant from the NIBIB titled, “Hyperspectral Single Photon Imaging.” This project is a collaboration between Meng, and Johns Hopkins University researchers, Yong Du and Eric Frey.