Hirschberg H, Wu G N, Madsen S J
Beckman Laser Institute, University of California, Irvine, CA 92612, USA.
Minim Invasive Neurosurg. 2007 Dec;50(6):318-23. doi: 10.1055/s-2007-993158.
The characteristics of an ideal contrast agent for use in the intraoperative MRI would be tumor-specificity and intracellular localization, combined with extended tumor enhancement, but with rapid elimination from the blood. The radiation sensitizing properties of Motexafin gadolinium (MGd) have been investigated in a number of clinical trials involving patients with brain metastases. These studies clearly show that MGd is detectable in magnetic resonance images many days following administration. The aim of this experimental study was to test whether Motexafin gadolinium (MGd) could serve as an efficient intraoperative contrast agent avoiding problems that arise with surgically induced intracranial enhancement.
F98 orthotopic brain tumors or surgical lesions were induced in Fisher rats. T1-weighted MRI studies were performed with either a single or multiple daily doses of MGd. The last contrast dose was administered either 7 or 24 hours prior to scanning in both tumor-bearing or surgically-treated animals. All scans were T1-weighted nce (TR=495 ms; TE=1 ms.) with a slice thickness of 1.0 mm. Three tubes containing 2.3, 0.23 and 0.023 mg/mL of MGd (in physiological saline) respectively, were used as standards to calibrate the scans.
Animals receiving either 30 or 60 mg/kg MGd i.v. developed clinical signs of impaired motor activity, and increasing lethargy and were euthanized 48 hours after MGd administration due to their poor and deteriorating condition. MGd given i.p. was tolerated up to a dose of 140 mg/kg. Despite multiple dosages and several administration modes (i.p., i.v.) no significant enhancement was observed if the scans were performed 7 or 24 hours following the last MGd dose. Clear enhancement was seen though when the scans were performed 30 min following MGd administration, indicating that the agent was being taken up by the tumor. Scans of necrotic lesions though were positive though 7 hours following MGd injection. MGd scans had no significant enhancement following surgically-induced lesions while scans with conventional contrast agents showed both meningeal and intraparenchymal enhancement.
This study suggests that MGd is not sequestered in viable tumor for the necessary time interval required to allow delayed imaging in this model. The agent does seem to remain in necrotic tissue for longer time intervals. MGd therefore would not be suitable as a contrast agent in intraoperative MRI for the detection of remaining tumor tissue during surgery.
用于术中磁共振成像（MRI）的理想造影剂应具备肿瘤特异性和细胞内定位特性，同时能增强肿瘤强化效果，并能迅速从血液中清除。钆喷替酸葡甲胺（MGd）的放射增敏特性已在多项涉及脑转移瘤患者的临床试验中进行了研究。这些研究清楚地表明，给药后数天在磁共振图像中仍可检测到MGd。本实验研究的目的是测试钆喷替酸葡甲胺（MGd）是否可作为一种有效的术中造影剂，避免手术引起的颅内强化所带来的问题。
在Fisher大鼠中诱导产生F98原位脑肿瘤或手术损伤。采用单次或每日多次剂量的MGd进行T1加权MRI研究。在荷瘤或手术治疗的动物中，最后一次造影剂剂量在扫描前7或24小时给药。所有扫描均为T1加权nce（TR = 495 ms；TE = 1 ms），层厚1.0 mm。分别含有2.3、0.23和0.023 mg/mL MGd（于生理盐水中）的三支试管用作校准扫描的标准物。
静脉注射30或60 mg/kg MGd的动物出现运动活动受损、嗜睡加重的临床症状，由于状况不佳且不断恶化，在给予MGd后48小时实施安乐死。腹腔注射MGd的耐受剂量高达140 mg/kg。尽管采用了多种剂量和多种给药方式（腹腔注射、静脉注射），但如果在最后一次给予MGd后7或24小时进行扫描，未观察到明显的强化。然而，在给予MGd后30分钟进行扫描时可见明显强化，表明该造影剂被肿瘤摄取。尽管在注射MGd后7小时坏死灶扫描呈阳性。MGd扫描在手术引起的损伤后无明显强化，而使用传统造影剂扫描时可见脑膜和脑实质强化。
本研究表明，在该模型中，MGd在活肿瘤中滞留的时间不足以进行延迟成像所需的必要时间间隔。该造影剂似乎在坏死组织中停留较长时间。因此，MGd不适用于术中MRI作为手术期间检测残留肿瘤组织的造影剂。
