Dynamic Change of Amide Proton Transfer Imaging in Irradiated Nasopharyngeal Carcinoma and Related Histopathological Mechanism

Mol Imaging Biol. 2021 Dec;23(6):846-853. doi: 10.1007/s11307-021-01607-y. Epub 2021 Apr 19.

Abstract

Objective: To investigate the dynamic change of amide proton transfer (APT) imaging before and after irradiation in nasopharyngeal carcinoma (NPC) and the underlying histopathological mechanism.

Materials and methods: Tumor-bearing BALB/C nude mouse models were established and randomly divided into three groups: high-dose group (20 Gy/2 fractions), low-dose group (10 Gy/2 fractions), and control group (0 Gy). MRI scanning was performed before irradiation and 3rd, 6th, and 9th day post-irradiation. Scanning sequence included T1 weighted, T2 weighted, and APT. HE staining and TUNEL immunofluorescence detection were performed to detect necrosis and apoptosis.

Results: After high-dose irradiation, the mean tumor APT values decreased significantly on the 3rd day and 6th day (from 3.83 before radiotherapy to 2.41%, P < 0.001, 3rd day; from 2.41 to 1.80%, P = 0.001, 6th day). For low-dose irradiation, the mean tumor APT values decreased slightly on the 3rd day and 6th day (from 3.52 to 3.13%, P = 0.109, 3rd day; from 3.13 to 3.05%, P = 0.64, 6th day). The mean APT values of nonirradiated tumor changed slightly. In contrast, the average volume of high-dose irradiated tumors did not decrease obviously until the 9th day post-irradiation (from 290 before radiotherapy to 208 mm3 on the 9th day). The low-dose irradiated tumors showed slow growth, and the nonirradiated tumors showed rapid growth. Subsequent HE staining and TUNEL staining showed obvious necrosis characteristics and higher proportion of positive apoptotic cell nucleus in high-dose irradiated tumors, but not nonirradiated tumors.

Conclusion: The APT signal intensity decreased after irradiation, which is earlier than the change of tumor volume. What is more, the decrease of APT signal intensity is more significant in high-dose group. Histological analysis showed obvious apoptosis and necrosis histological characteristic in irradiated tumor, which may explain the decrease of APT signal intensity. These results indicate that APT imaging has the potential to serve as a reliable biomarker for response assessment in NPC.

Keywords: Amide proton transfer; Nasopharyngeal carcinoma; Response evaluation; Tumor bearing mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides
  • Animals
  • Magnetic Resonance Imaging / methods
  • Mice
  • Mice, Inbred BALB C
  • Nasopharyngeal Carcinoma / radiotherapy
  • Nasopharyngeal Neoplasms* / diagnostic imaging
  • Nasopharyngeal Neoplasms* / radiotherapy
  • Protons*

Substances

  • Amides
  • Protons