Specific uptake of 99mTc-NC100692, an αvβ3-targeted imaging probe, in subcutaneous and orthotopic tumors.
Specific uptake of 99mTc-NC100692, an αvβ3-targeted imaging probe, in subcutaneous and orthotopic tumors.
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DOI：
10.1016/j.nucmedbio.2013.04.006
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发表时间：
2013-08
影响因子：
3.1
通讯作者：
Packard AB
中科院分区：
文献类型：
--
作者：
Dearling JL;Barnes JW;Panigrahy D;Zimmerman RE;Fahey F;Treves ST;Morrison MS;Kieran MW;Packard AB
αvβ3整合素是一种非常有吸引力的靶点，在血管生成上皮细胞和肿瘤细胞中均有表达。虽然αvβ3靶向治疗的最佳实施将需要先验识别靶点的存在，但这些化合物的临床评价通常不包括与αvβ3靶向诊断的平行研究。这至少部分是由于与用99 mTc标记的那些相比，PET放射性药物的可用性相对有限。为了开始解决这一局限性，我们评估了99 mTc-NC 100692的肿瘤摄取，99 mTc-NC 100692是一种环状RGD肽，在αvβ3阳性肿瘤模型中以约1 nM的亲和力与αvβ3结合，以及其体内特异性。MicroSPECT成像用于评估西仑吉肽（一种对αvβ3具有高亲和力的治疗剂）在原位U87胶质瘤肿瘤中阻断和置换99 mTc-NC 100692的能力。通过比较99 mTc-NC 100692与非特异性结构类似物99 mTc-AH-111744的生物分布，并通过用过量的未标记NC 100692阻断99 mTc-NC 100692的摄取，在荷皮下U87 MG肿瘤的小鼠中定量评价99 mTc-NC 100692的特异性。MicroSPECT成像研究表明，在颅内肿瘤模型中99 mTc-NC 100692的摄取被αvβ3靶向治疗性西仑吉肽阻断和取代。生物分布研究提供了这些成像结果的定量确认。注射后1小时，99 mTc-NC 100692的肿瘤摄取为2.8 ± 0.7% ID/g，而99 mTc-AH-111744为0.38 ± 0.1% ID/g（p < 0.001）。通过用过量的未标记的NC 100692预注射小鼠来阻断99 mTc-NC 100692摄取使肿瘤摄取减少约5倍，至0.68 ± 0.3%ID/g（p = 0.01）。这些结果证实，99 mTc-NC 100692确实靶向αvβ3，因此，可用于在抗αvβ3治疗前识别患者以及监测这些患者对治疗的反应。
The αvβ3 integrin, which is expressed by angiogenic epithelium and some tumor cells, is an attractive target for the development of both imaging agents and therapeutics. While optimal implementation of αvβ3-targeted therapeutics will require a priori identification of the presence of the target, the clinical evaluation of these compounds has typically not included parallel studies with αvβ3-targeted diagnostics. This is at least partly due to the relatively limited availability of PET radiopharmaceuticals in comparison to those labeled with 99mTc. In an effort to begin to address this limitation, we evaluated the tumor uptake of 99mTc-NC100692, a cyclic RGD peptide that binds to αvβ3 with ~1-nM affinity in an αvβ3-positive tumor model as well as its in vivo specificity. MicroSPECT imaging was used to assess the ability of cilengitide, a therapeutic with high affinity for αvβ3, to block and displace 99mTc-NC100692 in an orthotopic U87 glioma tumor. The specificity of 99mTc-NC100692 was quantitatively evaluated in mice bearing subcutaneous U87MG tumors, by comparison of the biodistribution of 99mTc-NC100692 with that of the non-specific structural analogue 99mTc-AH-111744 and by blocking uptake of 99mTc-NC100692 with excess unlabeled NC100692. MicroSPECT imaging studies demonstrated that uptake of 99mTc-NC100692 in the intracranial tumor model was both blocked and displaced by the αvβ3-targeted therapeutic cilengitide. Biodistribution studies provided quantitative confirmation of these imaging results. Tumor uptake of 99mTc-NC100692 at 1 h post-injection was 2.8 ± 0.7% ID/g compared to 0.38 ± 0.1% ID/g for 99mTc-AH-111744 (p < 0.001). Blocking 99mTc-NC100692 uptake by pre-injecting the mice with excess unlabeled NC100692 reduced tumor uptake by approximately fivefold, to 0.68 ± 0.3% ID/g (p = 0.01). These results confirm that 99mTc-NC100692 does, in fact, target the αvβ3 and may, therefore, be useful in identifying patients prior to anti-αvβ3 therapy as well as monitoring the response of these patients to therapy.
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影响因子：
4.7
作者：
Liu, S;Hsieh, WY;Mohammed, SI
通讯作者：
Mohammed, SI
新型 64Cu 和 68Ga 标记的 RGD 结合物可改善αvβ3 整合素表达的 PET 成像，且易于放射合成
影响因子：
9.3
作者：
Dumont, Rebecca A.;Deininger, Friederike;Fani, Melpomeni
通讯作者：
Fani, Melpomeni
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
1.3
作者：
Axelsson, Rimma;Bach-Gansmo, Tore;McParland, Brian J.
通讯作者：
McParland, Brian J.
影响因子：
5
作者：
Dobrucki LW;Tsutsumi Y;Kalinowski L;Dean J;Gavin M;Sen S;Mendizabal M;Sinusas AJ;Aikawa R
通讯作者：
Aikawa R