title: Kinetic studies with iodine-123-labeled serum amyloid P component in patients with systemic AA and AL amyloidosis and assessment of clinical value.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nuclear Medicine, University Hospital Groningen, The Netherlands.
authors.forename: P L
authors.initials: PL
authors.lastname: Jager
authors.forename: B P
authors.initials: BP
authors.lastname: Hazenberg
authors.forename: E J
authors.initials: EJ
authors.lastname: Franssen
authors.forename: P C
authors.initials: PC
authors.lastname: Limburg
authors.forename: M H
authors.initials: MH
authors.lastname: van Rijswijk
authors.forename: D A
authors.initials: DA
authors.lastname: Piers
mesh_terms: D000328:Adult; D000368:Aged; D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011877:Radionuclide Imaging; D000685:Serum Amyloid A Protein / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D000682:Amyloid; D007457:Iodine Radioisotopes; D000685:Serum Amyloid A Protein; D000683:Serum Amyloid P-Component; C035222:amyloid protein AL