[99mTc]Tc-labeled cyc-DX600-HYNIC as a SPECT probe for ACE2-specific pancreatic cancer imaging

Pan Zhou; Zheng Li; Danni Li; Shuai Xue; Rou Li; Lan Zhang; Qingyun Bai; Xiao Li

doi:10.62347/VFHT4078

[^99mTc]Tc-labeled cyc-DX600-HYNIC as a SPECT probe for ACE2-specific pancreatic cancer imaging

Am J Nucl Med Mol Imaging. 2024 Apr 25;14(2):122-133. doi: 10.62347/VFHT4078. eCollection 2024.

Authors

Pan Zhou^{1

2}, Zheng Li², Danni Li³, Shuai Xue^{1

2}, Rou Li³, Lan Zhang², Qingyun Bai¹, Xiao Li^{2

3

4}

Affiliations

¹ School of Chemistry and Bioengineering, Yichun University Yichun 336000, Jiangxi, China.
² Shanghai Institute of Applied Physics, Chinese Academy of Sciences Shanghai 201800, China.
³ Department of Nuclear Medicine, Shanghai Changhai Hospital Shanghai 200433, China.
⁴ Department of Nuclear Medicine, Pudong Hospital, Fudan University Shanghai 201399, China.

Abstract

As a regulator in renin-angiotensin-aldosterone system, angiotensin-converting enzyme 2 (ACE2) closely correlated with tumor progression of pancreatic cancer, meantime, was easily affected by a variety of factors. [^99mTc]Tc-cyc-DX600 SPECT was established as an ACE2-specific imaging protocol to figure out the ACE2 status in pancreatic tumor. BALB/C-NU mice were used to prepare the subcutaneous cell derived xenograft (CDX) models with HEK-293T or HEK-293T/hACE2 cells to validate ACE2 specificity of [^99mTc]Tc-cyc-DX600 SPECT and establish SPECT imaging protocol. On the basis of [^99mTc]Tc-cyc-DX600 SPECT and [¹⁸F]F-FDG PET/CT, ACE2-dependence on tumor size and tumor metabolism were further verified on orthotopic pancreatic cancer model with KPC cells. Immunohistochemical analysis was used to demonstrate the findings on ACE2 SPECT. [^99mTc]Tc-cyc-DX600 was of superior tumor uptake in HEK-293T/hACE2 CDX than wild type (6.74 ± 0.31 %ID/mL vs 1.83 ± 0.26 %ID/mL at 1.5 h post injection (p.i.); 3.14 ± 0.31 %ID/mL vs 1.16 ± 0.15 %ID/mL at 4.5 h p.i.). For the CDX models with PANC-1 cells, a significant negative correlation between the slope of tumor volume and tumor uptake was observed (r = -0.382 for the 1-4th day; r = -0.146 for the 1-5th day; r = -0.114 for the 1-6th day; r = -0.152 for the 1-7th day; but P > 0.05 for all). For orthotopic pancreatic cancer model, the linear correlation between FDG PET and ACE2 SPECT of the pancreatic lesions was negative (r = -0.878), the quantitative values of ACE2 SPCET was positively correlated with the volume of primary lesions (r = 0.752) and also positively correlated with the quantitative values of ACE2 immunohistochemical analysis (r = 0.991). Conclusively, [^99mTc]Tc-cyc-DX600 SPECT is an ACE2-specific imaging protocol with clinical translational potential, adding multidimensional information on the disease progression of pancreatic cancer.

Keywords: ACE2; [99mTc]Tc-cyc-DX600; functional imaging; pancreatic cancer; renin-angiotensin-aldosterone system; single photon emission computed tomography.