Bernhardt P, Benjegård S A, Kölby L, Johanson V, Nilsson O, Ahlman H, Forssell-Aronsson E
Department of Radiation Physics, Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, University of Göteborg, Göteborg, Sweden.
Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):514-24. doi: 10.1016/s0360-3016(01)01663-7.
Therapy of tumors expressing somatostatin receptors, sstr, has recently been clinically tested using somatostatin analogues labeled with (111)In and (90)Y. Several other radionuclides, i.e., (131)I, (161)Tb, (64)Cu, (188)Re, (177)Lu, and (67)Ga, have also been proposed for this type of therapy. The aim of this work was to investigate the usefulness of the above-mentioned radionuclides bound to somatostatin analogues for tumor therapy.
Biokinetic data of (111)In-labeled octreotide in mice and man were used, primarily from our studies but sometimes from the literature. Dosimetric calculations were performed with the assumption that biokinetics were similar for all radionuclides bound to somatostatin analogues. The cumulated tumor:normal-tissue activity concentration, TNC was calculated for the various physical half-lives of the radionuclides. Using mathematical models, the tumor:normal-tissue mean absorbed dose rate ratio, TN D and tumor:normal-tissue mean absorbed dose ratio, TND, were calculated for various tumor sizes in mice and humans.
TNC of radionuclide-labeled octreotide increased with physical half-life for most organs, both in mice and in humans. TN D showed that radionuclides emitting electrons with too high energy are not suitable for therapy of small tumors. Furthermore, radionuclides with a higher frequency of photon emissions relative to electron emissions will yield lower TN D and are thus less suitable for therapy than radionuclides with a lower frequency of photon emissions. The TND was highest for (161)Tb in both mice and humans.
The results demonstrate that long-lived radionuclides, which emit electrons with rather low energy and which have low frequency of photon emissions, should be the preferred therapy for disseminated small sstr-expressing tumors.
最近已使用用(111)铟和(90)钇标记的生长抑素类似物对表达生长抑素受体(sstr)的肿瘤进行了临床治疗测试。还提出了几种其他放射性核素,即(131)碘、(161)铽、(64)铜、(188)铼、(177)镥和(67)镓用于此类治疗。这项工作的目的是研究与生长抑素类似物结合的上述放射性核素在肿瘤治疗中的实用性。
使用了(111)铟标记的奥曲肽在小鼠和人体中的生物动力学数据,主要来自我们的研究,但有时也来自文献。剂量学计算是在假设与生长抑素类似物结合的所有放射性核素的生物动力学相似的情况下进行的。针对放射性核素的各种物理半衰期计算了累积肿瘤:正常组织活度浓度(TNC)。使用数学模型,针对小鼠和人类的各种肿瘤大小计算了肿瘤:正常组织平均吸收剂量率比(TND)和肿瘤:正常组织平均吸收剂量比(TND)。
放射性核素标记的奥曲肽的TNC在大多数器官中随物理半衰期增加,在小鼠和人体中均如此。TND表明发射能量过高电子的放射性核素不适用于小肿瘤的治疗。此外,相对于电子发射具有较高光子发射频率的放射性核素将产生较低的TND,因此比具有较低光子发射频率的放射性核素更不适用于治疗。在小鼠和人体中,(161)铽的TND最高。
结果表明,发射能量相当低且光子发射频率低的长寿命放射性核素应是播散性小的表达sstr肿瘤的首选治疗方法。