对系统性AA型和AL型淀粉样变性患者进行碘-123标记血清淀粉样蛋白P成分的动力学研究及临床价值评估。

Kinetic studies with iodine-123-labeled serum amyloid P component in patients with systemic AA and AL amyloidosis and assessment of clinical value.

作者信息

Jager P L, Hazenberg B P, Franssen E J, Limburg P C, van Rijswijk M H, Piers D A

机构信息

Department of Nuclear Medicine, University Hospital Groningen, The Netherlands.

出版信息

J Nucl Med. 1998 Apr;39(4):699-706.

PMID:9544684

Abstract

UNLABELLED

In systemic amyloidosis, widespread amyloid deposition interferes with organ function, frequently with fatal consequences. Diagnosis rests on demonstrating amyloid deposits in the tissues, traditionally with histology although scintigraphic imaging with radiolabeled serum amyloid P component (SAP) has lately been developed as a specific noninvasive alternative. We report a detailed analysis of the abnormal turnover of SAP in patients with systemic amyloidosis and an assessment of its clinical value.

METHODS

Iodine-123-labeled human SAP (200 MBq) SAP was injected intravenously into 49 patients with histologically proven systemic AA- or AL- amyloidosis and in 7 control subjects. Plasma clearance and whole-body retention of labeled SAP were analyzed over 48 hr using plasma sampling, whole-body gamma camera imaging and measurement of radioactivity in the urine. The rate of SAP synthesis and interstitial exchange were determined, and the size of the amyloid compartment was compared with clinical estimates of whole-body amyloid load and patient survival.

RESULTS

All plasma time-activity curves were biphasic. In comparison with control subjects, patients with amyloidosis showed significantly faster plasma disappearance [4-hr value: AA 48% +/- 18%, AL 45% +/- 15% versus 65% +/- 8% (p < 0.05)], higher total-body retention 48 hr p.i. [AA 74% +/- 14%, AL 73% +/- 17% versus 46% +/- 15% (p < 0.01)] and especially higher extravascular retention 48 hr p.i. [AA 59% +/- 16%, AL 58% +/- 19% versus 30% +/- 14% (p < 0.01)]. Extravascular retention correlated with clinical estimation of the amyloid load. If extravascular retention values in patients with AL amyloidosis were over 60%, survival was decreased (median 4 versus 23 mo, p < 0.001). Markedly increased interstitial exchange rates were present in amyloidosis (AA 64 +/- 61, AL 50 +/- 37 versus 18 +/- 8 mg/hr), whereas the SAP synthesis rate did not differ from the control values (AA 5.0 +/- 3.0, AL 5.5 +/- 3.2 versus 4.5 +/- 1.4 mg/hr).

CONCLUSION

The presence of systemic amyloidosis is characterized by accelerated initial clearance of 123I-SAP from the plasma and increased interstitial exchange rate and extravascular retention. These findings reflect reversible binding of radiolabeled SAP to amyloid deposits and provide clinically useful information for diagnosis, monitoring of therapy and prognosis in patients with systemic amyloidosis.

摘要

未标记

在系统性淀粉样变性中，广泛的淀粉样蛋白沉积会干扰器官功能，常常导致致命后果。诊断依赖于在组织中证实淀粉样蛋白沉积，传统上通过组织学检查，尽管最近已开发出用放射性标记的血清淀粉样蛋白P成分（SAP）进行闪烁成像作为一种特定的非侵入性替代方法。我们报告了对系统性淀粉样变性患者中SAP异常周转的详细分析及其临床价值评估。

方法

将碘-123标记的人SAP（200MBq）静脉注射到49例经组织学证实为系统性AA型或AL型淀粉样变性的患者以及7名对照受试者中。使用血浆采样、全身γ相机成像和尿液放射性测量，在48小时内分析标记SAP的血浆清除率和全身滞留情况。测定SAP合成率和间质交换率，并将淀粉样蛋白区室的大小与全身淀粉样蛋白负荷的临床估计值和患者生存率进行比较。

结果

所有血浆时间-活性曲线均为双相。与对照受试者相比，淀粉样变性患者的血浆消失明显更快[4小时值：AA型48%±18%，AL型45%±15%，而对照为65%±8%（p<0.05）]，注射后48小时全身滞留率更高[AA型74%±14%，AL型73%±17%，而对照为46%±15%（p<0.01）]，尤其是注射后48小时血管外滞留率更高[AA型59%±16%，AL型58%±19%，而对照为30%±14%（p<0.01）]。血管外滞留与淀粉样蛋白负荷的临床估计值相关。如果AL型淀粉样变性患者的血管外滞留值超过60%，生存率会降低（中位数4个月对23个月，p<0.001）。淀粉样变性患者的间质交换率明显增加（AA型64±61，AL型50±37，而对照为18±8mg/小时），而SAP合成率与对照值无差异（AA型5.0±3.0，AL型5.5±3.2，而对照为4.5±1.4mg/小时）。