Non-invasive assessment of tumour cell proliferation with positron emission tomography and [76Br]bromodeoxyuridine

Area of Science:

• Oncology
• Nuclear Medicine
• Medical Imaging

Background:

• Non-invasive methods for assessing preclinical therapeutic response are crucial in oncology.
• Cell proliferation, particularly the growth fraction, is a key indicator of tumor response.
• Thymidine incorporation into DNA of S-phase cells is a standard method for assessing proliferation.

Purpose of the Study:

• To evaluate the utility of bromide-76 (76Br) labeled bromodeoxyuridine ([76Br]BrUdR) in positron emission tomography (PET) for assessing cell proliferation in metastatic melanoma.
• To compare [76Br]BrUdR PET findings with immunohistochemical assessments of proliferation.

Main Methods:

• Seven patients with metastatic melanoma underwent [76Br]BrUdR PET scans.
• Ex vivo immunohistochemistry using anti-bromo-deoxyuridine and MIB-1 antibodies was performed on metastases.
• Blood samples were analyzed to determine the kinetics of the radiopharmaceutical.

Main Results:

• [76Br]BrUdR PET accumulation showed a significant correlation with immunohistochemically determined S-phase and cycling cells.
• One patient had an unexpected metastasis detected by [76Br]BrUdR-PET.
• Fast debromation of [76Br]BrUdR led to high background activity, suggesting increased circulation rather than incorporation into proliferating cells.

Conclusions:

• While [76Br]BrUdR PET showed correlation with proliferation markers, its clinical utility is limited by rapid debromation and high background activity.
• The observed signal may primarily reflect increased blood flow in rapidly proliferating metastases rather than direct incorporation into DNA.
• Further development is needed to overcome the limitations for accurate cell proliferation assessment in vivo.