KINETIC-STUDIES WITH IODINE-123-LABELED SERUM AMYLOID P COMPONENT IN PATIENTS WITH SYSTEMIC AA AND AL AMYLOIDOSIS AND ASSESSMENT OF CLINICAL-VALUE

In systemic amyloidosis, widespread amyloid deposition interferes with organ function, frequently with fatal consequences. Diagnosis rests o n demonstrating amyloid deposits in the tissues, traditionally with hi stology 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 o f SAP in patients with systemic amyloidosis and an assessment of its c linical value, Methods: iodine-123-labeled human SAP (200 MBq) SAP was injected intravenously into 49 patients with histologically proven sy stemic AA- or AL- amyloidosis and in 7 control subjects, Plasma cleara nce and whole-body retention of labeled SAP were analyzed over 48 hr u sing plasma sampling, whole-body gamma camera imaging and measurement of radioactivity in the urine, The rate of SAP synthesis and interstit ial exchange were determined, and the size of the amyloid compartment was compared with clinical estimates of whole-body amyloid load and pa tient survival. Results: Ail plasma time-activity curves were biphasic . In comparison with control subjects, patients with amyloidosis showe d significantly faster plasma disappearance [4-hr value: AA 48% +/- 18 %, AL 45% +/- 15% versus 65% +/- 8% (p < 0.05)], higher total-body ret ention 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. [A A 59% +/- 16%, AL 58% +/- 19% versus 30% +/- 14% (p < 0.01)], Extravas cular retention correlated with clinical estimation of the amyloid loa d, If extravascular retention values in patients with AL amyloidosis w ere over 60%, survival was decreased (median 4 versus 23 mo, p < 0.001 ), Markedly increased interstitial exchange rates were present in amyl oidosis (AA 64 +/- 61, AL 50 +/- 37 versus 18 +/- 8 mg/hr), whereas th e 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 prese nce of systemic amyloidosis is characterized by accelerated initial cl earance of I-123-SAP from the plasma and increased interstitial exchan ge rate and extravascular retention. These findings reflect reversible binding of radiolabeled SAP to amyloid deposits and provide clinicall y useful information for diagnosis, monitoring of therapy and prognosi s in patients with systemic amyloidosis.