[논문]Dual-Modality Imaging of Prostate Cancer with a Fluorescent and Radiogallium-Labeled Gastrin-Releasing Peptide Receptor Antagonist

Zhang, Hanwen; Desai, Pooja; Koike, Yusuke; Houghton, Jacob; Carlin, Sean; Tandon, Nidhi; Touijer, Karim; Weber, Wolfgang A.

doi:10.2967/jnumed.116.176099

Dual-Modality Imaging of Prostate Cancer with a Fluorescent and Radiogallium-Labeled Gastrin-Releasing Peptide Receptor Antagonist 원문보기

The Journal of nuclear medicine : JNM, v.58 no.1, 2017년, pp.29 - 35

Zhang, Hanwen (Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York) , Desai, Pooja (Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York) , Koike, Yusuke (Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York) , Houghton, Jacob (Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York) , Carlin, Sean (Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York) , Tandon, Nidhi (Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York) , Touijer, Karim (Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York) , Weber, Wolfgang A. (and)

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Gastrin-releasing peptide (GRP) receptors (GRPr) are frequently overexpressed in human prostate cancer, and radiolabeled GRPr affinity ligands have shown promise for in vivo imaging of prostate cancer with PET. The goal of this study was to develop a dual-modality imaging probe that can be used for noninvasive PET imaging and optical imaging of prostate cancer. Methods: We designed and synthesized an IRDye 650 and DOTA-conjugated GRPr antagonist, HZ220 (DOTA-Lys(IRDye 650)-PEG4-[D-Phe6, Sta13]-BN(6-14)NH2), by reacting DOTA-Lys-PEG4-[D-Phe6, Sta13]-BN(6-14)NH2 (HZ219) with IRDye 650 N-hydroxysuccinimide (NHS) ester. Receptor-specific binding of gallium-labeled HZ220 was characterized in PC-3 prostate cancer cells (PC-3), and tumor uptake in mice was imaged with PET/CT and fluorescence imaging. Receptor binding affinity, in vivo tumor uptake, and biodistribution were compared with the GRPr antagonists HZ219, DOTA-PEG4-[D-Phe6, Sta13]-BN(6-14)NH2 (DOTA-AR), and DOTA-(4-amino-1-carboxymethyl-piperidine)-[D-Phe6, Sta13]-BN(6-14)NH2 (DOTA-RM2). Results: After hydrophilic–lipophilic balance cartridge purification, 68Ga-HZ220 was obtained with a radiochemical yield of 56% ± 8% (non–decay-corrected), and the radiochemical purity was greater than 95%. Ga-HZ220 had a lower affinity for GRPr (inhibitory concentration of 50% [IC50], 21.4 ± 7.4 nM) than Ga-DOTA-AR (IC50, 0.48 ± 0.18 nM) or Ga-HZ219 (IC50, 0.69 ± 0.18 nM). Nevertheless, 68Ga-HZ220 had an in vivo tumor accumulation similar to 68Ga-DOTA-AR (4.63 ± 0.31 vs. 4.07 ± 0.29 percentage injected activity per mL [%IA/mL] at 1 h after injection) but lower than that of 68Ga-DOTA-RM2 (10.4 ± 0.4 %IA/mL). The tumor uptake of 68Ga-HZ220 was blocked significantly with an excessive amount of GRP antagonists. IVIS spectrum imaging also visualized PC-3 xenografts in vivo and ex vivo with a high-contrast ratio. Autoradiography and fluorescent-based microscopic imaging with 68Ga-HZ220 consistently colocated the expression of GRPr. 68Ga-HZ220 displayed a higher kidney uptake than both 68Ga-DOTA-AR and 68Ga-DOTA-RM2 (16.9 ± 6.5 vs. 4.48 ± 1.63 vs. 5.01 ± 2.29 %IA/mL). Conclusion: 68Ga-HZ220 is a promising bimodal ligand for noninvasive PET imaging and intraoperative optical imaging of GRPr-expressing malignancies. Bimodal nuclear/fluorescence imaging may not only improve cancer detection and guide surgical resections, but also improve our understanding of the uptake of GRPr ligands on the cellular level.

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Dual-Modality Imaging of Prostate Cancer with a Fluorescent and Radiogallium-Labeled Gastrin-Releasing Peptide Receptor Antagonist 원문보기

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