Samnick Samuel, Romeike Bernd F M, Kubuschok Boris, Hellwig Dirk, Amon Michaela, Feiden Wolfgang, Menger Michael D, Kirsch Carl-Martin
Department of Nuclear Medicine, Saarland University Medical Center, 66421 Homburg/Saar, Germany.
Eur J Nucl Med Mol Imaging. 2004 Apr;31(4):532-41. doi: 10.1007/s00259-003-1445-1. Epub 2004 Jan 14.
Pancreatic cancer is associated with the worst 5-year survival rate of any human cancer. This high mortality is due, in part, to difficulties in establishing early and accurate diagnosis. Because most tumours share the ability to accumulate amino acids more effectively than normal tissues and any other pathology, assessment of amino acid transport in tumour cells using radiolabelled amino acids has become one of the most promising tools for tumour imaging. This study investigated the potential of p-[(123)I]iodo-L-phenylalanine (IPA) for detection of pancreatic cancer by single-photon emission tomography. IPA affinity for pancreatic tumour was investigated in human pancreatic adenocarcinoma PaCa44 and PanC1 cells, followed by analysis of the underlying mechanisms of tracer accumulation in neoplastic cells. Thereafter, IPA was evaluated for targeting of pancreatic tumours using SCID mice engrafted with primary human pancreatic adenocarcinoma cells, as well as in acute inflammation models in immunocompetent mice and rats. IPA accumulated intensively in human pancreatic tumour cells. Radioactivity accumulation in tumour cells following a 30-min incubation at 37 degrees C/pH 7.4 varied from 41% to 58% of the total loaded activity per 10(6) cells. The cellular uptake was temperature and pH dependent and predominantly mediated by specific carriers for neutral amino acids, namely the sodium-independent and L-leucine-preferring (L-system) transporter and the alanine-, serine- and cysteine-preferring (ASC-system) transporter. Protein incorporation was less than 8%. Biodistribution studies showed rapid localization of the tracer to tumours, reaching 10%+/-2.5% to 15%+/-3% of the injected dose per gram (I.D./g) in heterotopic tumours compared with 17%+/-3.5% to 22%+/-4.3% I.D./g in the orthotopic tumours, at 60 and 240 min post injection of IPA, respectively. In contrast, IPA uptake in the gastrointestinal tract and areas of inflammation remained moderate and decreased with time. Excellent tumour detection was obtained by gamma camera imaging. The specific and high-level targeting of IPA to tumour and the negligible uptake in the gastrointestinal tract and areas of inflammation indicate that p-[(123)I]iodo-L-phenylalanine is a promising tracer for differential diagnosis of pancreatic cancer.
胰腺癌是所有人类癌症中5年生存率最差的。这种高死亡率部分归因于早期准确诊断的困难。由于大多数肿瘤比正常组织和任何其他病理情况更有效地积累氨基酸，使用放射性标记氨基酸评估肿瘤细胞中的氨基酸转运已成为肿瘤成像最有前景的工具之一。本研究通过单光子发射断层扫描研究了对 - [（123）I]碘 - L - 苯丙氨酸（IPA）检测胰腺癌的潜力。在人胰腺腺癌PaCa44和PanC1细胞中研究了IPA对胰腺肿瘤的亲和力，随后分析了示踪剂在肿瘤细胞中积累的潜在机制。此后，使用植入原发性人胰腺腺癌细胞的SCID小鼠以及免疫活性小鼠和大鼠的急性炎症模型评估IPA对胰腺肿瘤的靶向性。IPA在人胰腺肿瘤细胞中大量积累。在37℃/pH 7.4孵育30分钟后，每10（6）个细胞中肿瘤细胞的放射性积累占总加载活性的41％至58％。细胞摄取取决于温度和pH，主要由中性氨基酸的特异性载体介导，即不依赖钠且优先摄取L - 亮氨酸的（L - 系统）转运体和优先摄取丙氨酸、丝氨酸和半胱氨酸的（ASC - 系统）转运体。蛋白质掺入率小于8％。生物分布研究表明，示踪剂在肿瘤中迅速定位，在注射IPA后60分钟和240分钟时，异位肿瘤中每克注射剂量（I.D./g）达到10％±2.5％至15％±3％，而原位肿瘤中为17％±3.5％至22％±4.3％I.D./g。相比之下，胃肠道和炎症区域对IPA的摄取保持中等水平并随时间下降。通过γ相机成像获得了出色的肿瘤检测效果。IPA对肿瘤的特异性和高水平靶向以及在胃肠道和炎症区域的可忽略不计的摄取表明，对 - [（123）I]碘 - L - 苯丙氨酸是一种有前景的用于胰腺癌鉴别诊断的示踪剂。
