Department of Radiology, Kimmel Cancer Center, Philadelphia, Pennsylvania, USA.
J Nucl Med. 2010 Jan;51(1):106-11. doi: 10.2967/jnumed.109.069542. Epub 2009 Dec 15.
Despite the great strides made in imaging breast cancer (BC) in humans, the current imaging modalities miss up to 30% of BC, do not distinguish malignant lesions from benign ones, and require histologic examinations for which invasive biopsy must be performed. Annually in the United States, approximately 5.6 million biopsies find benign lesions. More than 50% of human BCs overexpress cyclin D1, and all BCs exhibit VPAC1 oncogene products. Together, these gene products may provide an excellent biomarker for the early and accurate detection of BC. We have evaluated 4 biologically active peptide analogs that have high affinity for VPAC1. The transgenic MMTVneu mice spontaneously develop BC and metastatic lesions that overexpress cyclin D1 and VPAC1 biomarkers. The MMTVneu mouse, therefore, provides an excellent animal model that mimics the pathogenesis of human BC. The objective of this investigation was to determine the ability of 1 of the peptide analogs, (64)Cu-TP3805, to detect BC in MMTVneu mice using (18)F-FDG as a gold standard.
The transgenic MMTVneu mouse colony was maintained. Offspring were screened for transgenic status by reverse transcriptase polymerase chain reaction (RT-PCR). Nine mice with visible, palpable, or unknown metastatic lesions were entered into the protocol. (18)F-FDG (6,475 +/- 1,628 kBq [175 +/- 44 microCi]) PET served as a control, followed by a CT scan and 24-48 h later by PET with (64)Cu-TP3805 (4,588 +/- 962 kBq [124 +/- 26 microCi]). RT-PCR on excised tumors determined VPAC1 expression, and histology ascertained the pathology.
Ten tumors were detected by PET. Four tumors were detected both by (18)F-FDG and by (64)Cu-TP3805. Additionally, 4 tumors were imaged with (64)Cu-TP3805 only. These 8 tumors overexpressed VPAC1 receptors and were malignant by histology. The 2 remaining tumors were visualized with (18)F-FDG only. These tumors did not express the VPAC1 oncogene product and had benign histology. The standard uptake value ranged from 3.1 to 18.3 for (64)Cu-TP3805 and 0.9 to 1.4 for (18)F-FDG.
(64)Cu-TP3805 identified all malignant lesions unequivocally that overexpressed the VPAC1 oncogene surface product. The 2 benign tumors that did not express the VPAC1 receptor were not imaged. (64)Cu-TP3805 promises to have the potential for the early and accurate imaging of primary and metastatic BC.
确定使用 1 种肽类似物 (64)Cu-TP3805 检测 MMTVneu 小鼠乳腺癌的能力，以 (18)F-FDG 作为金标准。
维持转基因 MMTVneu 小鼠群体。通过逆转录聚合酶链反应 (RT-PCR) 筛选后代的转基因状态。将 9 只具有可见、可触及或未知转移性病变的小鼠纳入方案。(18)F-FDG(6475 ± 1628 kBq[175 ± 44 μCi]) PET 作为对照，随后进行 CT 扫描，24-48 小时后进行 (64)Cu-TP3805(PET) 扫描 (4588 ± 962 kBq[124 ± 26 μCi])。切除肿瘤的 RT-PCR 确定 VPAC1 表达，组织学确定病理学。
10 个肿瘤通过 PET 检测到。4 个肿瘤通过 (18)F-FDG 和 (64)Cu-TP3805 均被检测到。此外，用 (64)Cu-TP3805 还可以对 4 个肿瘤进行成像。这 8 个肿瘤过表达 VPAC1 受体，组织学上为恶性肿瘤。剩下的 2 个肿瘤仅用 (18)F-FDG 显示。这些肿瘤没有表达 VPAC1 癌基因产物，组织学为良性。(64)Cu-TP3805 的标准摄取值范围为 3.1-18.3，(18)F-FDG 的标准摄取值范围为 0.9-1.4。
(64)Cu-TP3805 明确识别了所有过表达 VPAC1 癌基因表面产物的恶性病变。2 个不表达 VPAC1 受体的良性肿瘤未成像。(64)Cu-TP3805 有望具有早期、准确成像原发性和转移性乳腺癌的潜力。
