Slooter Gerrit D, Aalbers Arend G J, Breeman Wouter A P, Hiemstra Coen A, Marquet Richard L, Krenning Eric P, van Eijck Casper H J
Department of Surgery, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
J Nucl Med. 2002 Dec;43(12):1681-7.
The aim of this animal study was to evaluate whether peptide receptor radionuclide therapy with (111)In-diethylenetriaminepentaacetic acid (DTPA)(0)-octreotide was able to reduce tumor growth even under tumor growth-stimulating conditions induced by partial hepatectomy (PHx).
Rats underwent 70% PHx or sham operation. The development of hepatic metastases was determined 21 d after direct injection of somatostatin receptor (SS-R)-positive or SS-R-negative tumor cells into the portal vein. Groups of 8 or 9 animals that underwent PHx or sham operation were treated with octreotide 50 micro g/kg subcutaneously twice daily or with 370 MBq (111)In-DTPA(0)-octreotide intravenously on days 1 and 8. Both treatments were compared with control treatment. Forty non-tumor-bearing rats were used to determine the influence of (111)In-DTPA(0)-octreotide therapy on liver regeneration after PHx.
PHx induced an increase in tumor growth in all experiments (P < 0.01). Octreotide treatment did not influence tumor growth after PHx or sham operation. (111)In-DTPA(0)-octreotide could effectively reduce tumor growth in the liver of SS-R-positive tumors also under conditions of increased tumor growth as generated by PHx (P < 0.01). (111)In-DTPA(0)-octreotide was also effective on SS-R-negative tumors after PHx (P = 0.01) but not after sham operation. Furthermore, (111)In-DTPA(0)-octreotide therapy did not influence liver regeneration or liver function after PHx.
Peptide receptor radionuclide therapy with (111)In-DTPA(0)-octreotide is effective in SS-R-positive tumors. During liver regeneration, the growth of SS-R-negative tumors is also reduced. This effect is not induced by impairment of liver regeneration or liver function. Radionuclide therapy could therefore be a promising treatment modality for patients with symptomatic liver metastases of neuroendocrine tumors in combination with liver resection.
本动物研究的目的是评估用（111）铟 - 二乙三胺五乙酸（DTPA）（0） - 奥曲肽进行肽受体放射性核素治疗是否能够在部分肝切除术（PHx）诱导的肿瘤生长刺激条件下仍能减少肿瘤生长。
大鼠接受70%肝部分切除术或假手术。在将生长抑素受体（SS - R）阳性或SS - R阴性肿瘤细胞直接注入门静脉21天后，确定肝转移的发生情况。接受肝部分切除术或假手术的8或9只动物组，在第1天和第8天每天两次皮下注射50μg/kg奥曲肽或静脉注射370MBq（111）铟 - DTPA（0） - 奥曲肽。将这两种治疗方法与对照治疗进行比较。使用40只未荷瘤大鼠来确定（111）铟 - DTPA（0） - 奥曲肽治疗对肝部分切除术后肝脏再生的影响。
在所有实验中，肝部分切除术均诱导肿瘤生长增加（P < 0.01）。奥曲肽治疗对肝部分切除术或假手术后的肿瘤生长没有影响。（111）铟 - DTPA（0） - 奥曲肽在肝部分切除术所产生的肿瘤生长增加的情况下，也能有效减少SS - R阳性肿瘤在肝脏中的生长（P < 0.01）。（111）铟 - DTPA（0） - 奥曲肽对肝部分切除术后的SS - R阴性肿瘤也有效（P = 0.01），但对假手术后的肿瘤无效。此外，（111）铟 - DTPA（0） - 奥曲肽治疗对肝部分切除术后的肝脏再生或肝功能没有影响。
用（111）铟 - DTPA（0） - 奥曲肽进行肽受体放射性核素治疗对SS - R阳性肿瘤有效。在肝脏再生过程中，SS - R阴性肿瘤的生长也会减少。这种效应不是由肝脏再生或肝功能受损引起 的。因此，放射性核素治疗可能是神经内分泌肿瘤有症状肝转移患者联合肝切除的一种有前景的治疗方式。
