Kanazawa University research: Tracing tumors: targeting and imaging cancer cells

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Apr 27, 2021, 03:19 ET

KANAZAWA, Japan, April 27, 2021 /PRNewswire/ -- In a recent study published in the journal Molecules researchers at Kanazawa University describe the use of novel gallium-based radiotracers to visualize tumors in the body.

Cancer cells highly express specific proteins on their surface which helps oncologists identify and target these cells. For example, platelet-derived growth factor receptor β (PDGFRβ) which is often found on breast and colon cancer cells has been used to design probes that can attach to it and facilitate imaging of these cells. All such tracers designed to date have shown low accumulation within tumor tissues making it hard to visualize the cancer accurately. However, a team led by Kazuma Ogawa at Kanazawa University has now used radiolabeled gallium (Ga) to create tracers which showed potential when tested in mice.

Typical imaging tracers consist of three segments: a bait molecule designed to bind to the target (PDGFRβ in this case); a radioactive molecule that facilitates imaging; and a linker molecule that connects the other two. In their study, the researchers adopted peptides designed to attach to PDGFRβ. Peptides are miniature proteins that quickly hustle into different organs in the body without attracting much attention from the immune system. For the next segment, an atomic form of gallium known as ⁶⁷Ga, which is an alternative radionuclide instead of ⁶⁸Ga, was used. ⁶⁸Ga can emit radiations which are picked up on a PET scan—a high-resolution imaging technique. The two segments were connected using either of six different linkers, creating a total of seven peptide-based tracers (one had no linker). After synthesis, radiochemical yields and satisfactory purities of all the tracers were first confirmed.

The stability of these tracers was then examined in buffer and murine plasma. Two tracers, namely, [⁶⁷Ga]27 and [⁶⁷Ga]28 exhibited highest levels of stability. These two tracers also showed high uptake when incubated with cancer cells. To investigate them deeper, [⁶⁷Ga]27 and [⁶⁷Ga]28 were injected into tumor-bearing mice. While the tumor accumulation was not as high as expected, within an hour, almost twice as much of each tracer was present within tumor tissues than in the blood. The tracers were also less predominant in non-tumorous organs indicating their potential for accurate imaging. When peptide as blocking agent and [⁶⁷Ga]27 were co-injected into the tumor-bearing mice, the tumor-to-blood ratio was significantly decreased. This result indicates the accumulation of [⁶⁷Ga]27 in tumor is PDGFRβ specific.

[⁶⁷Ga]27 and [⁶⁷Ga]28 show promise in cancer detection and treatment monitoring due to their success in reaching tumor sites. There are, however, still several steps before we may see them being used as a diagnostic aid for patients. "Further structural modification to increase the accumulation of the tracer in the PDGFRβ-positive tumors is necessary for effective in vivo imaging," reports the team.

Background

Gallium scans and positron emission tomography (PET) – Two atomic forms of the element gallium, ⁶⁷Ga and ⁶⁸Ga, are used in medical imaging because of their radioactive properties. Both these forms of gallium are unstable and emit radiation which is easy to pick up on different scans. ⁶⁷Ga predominantly emits gamma rays, while ⁶⁸Ga emits atomic particles known as positrons. Annihilation radiations born from these positrons are detected on a PET machine and used for visualizing target organs.⁶⁷Ga has longer half-life (3.3 days) than ⁶⁸Ga (68 min). Thus, for this preliminary investigation the team used ⁶⁷Ga to first construct the tracers and evaluate them.

Reference

Nurmaya Effendi, Kenji Mishiro, Kazuhiro Shiba, Seigo Kinuya, Kazuma Ogawa. Development of Radiogallium-Labeled Peptides for Platelet-Derived Growth Factor Receptor b (PDGFRb) Imaging: Influence of Different Linkers. Molecules, 2021.

Link to related figure

https://www.kanazawa-u.ac.jp/wp-content/uploads/2021/04/210413_Figure1.png

Caption: Design of study. Rradiotracers targeting PDGFRβ, ⁶⁷Ga-DOTA-(linker)-IPLPPPRRPFFK peptides, were designed, synthesized, and evaluated. (ᴅ-alanine)₃, (ᴅ-alanine)₅, (β-alanine)₂, (β-alanine)₄, (ethylene glycol)₂, or (ethylene glycol)₄ was inserted between the IPLPPPRRPFFK peptide N-terminus and Ga-DOTA complex.

Contact details

Mr Tomoya Sato
Kanazawa University, Frontier Science and Social Co-creation Initiative
Kakuma, Kanazawa, Ishikawa, 920-1192, JAPAN
EMAIL: [email protected]
Telephone: 81-762-645-076

About Kanazawa University

http://www.kanazawa-u.ac.jp/e/

As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities.

The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas.

SOURCE Kanazawa University