title: Quantification of lymphatic function for investigation of lymphedema: depot clearance and rate of appearance of soluble macromolecules in blood.
abstract: The object of this study was to develop a new technique for the quantitative measurement of lymphatic function. The rate of clearance of radiolabeled protein from a subcutaneous depot is supplemented by measurement of the appearance of the protein in venous blood. This initial study was performed on normal arms, with a view to subsequent clinical application such as in the investigation of women with breast cancer--related lymphedema (BCRL).
  
  
  METHODS
  Fourteen healthy volunteers (12 women, 2 men) and 8 women awaiting surgery for breast cancer were recruited for the study. Each received subcutaneous depot injection of protein solution in the second dorsal web space of each hand, labeled with (111)In on one side and with (99m)Tc on the other side. Human serum albumin (HSA) was the protein used in the first 8 subjects and human polyclonal immunoglobulin G (HIgG) was used thereafter. The activity at each depot was measured at regular intervals using a collimated sodium iodide scintillation detector, and the activity in venous blood sampled from both arms was measured in an automatic sample counter.
  
  
  RESULTS
  (99m)Tc-HSA cleared from the depot consistently faster than (111)In-HSA (P = 0.001). The proportions of radionuclide remaining bound to protein in venous blood were higher for (99m)Tc than for (111)In. HIgG displayed improved labeling stability for both nuclides, reflected in equal rates of clearance. Blood activity rose steadily after an early latent phase and for HIgG correlated strongly with the rate of clearance from the depot (P < 0.001). Marked variation between individuals was observed.
  
  
  CONCLUSIONS
  A dual-isotope technique relies on identical behavior of the 2 radiopharmaceuticals used. This study shows that this is the case with respect to HIgG but not HSA. (99m)Tc-HSA cleared faster than (111)In-HSA and yet displayed better in vivo labeling stability. We conclude that (111)In dissociates from HSA in the depot but then becomes locally bound. Using HIgG, a close correlation was observed between the rates of clearance from the depot and the appearance in venous blood. This finding suggests that HIgG would be a suitable marker for subsequent dual-isotope studies on women with BCRL.
authors.affiliation: Cambridge Breast Unit, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Pain
authors.forename: R Steven
authors.initials: RS
authors.lastname: Nicholas
authors.forename: Robert W
authors.initials: RW
authors.lastname: Barber
authors.forename: James R
authors.initials: JR
authors.lastname: Ballinger
authors.forename: Arnie D
authors.initials: AD
authors.lastname: Purushotham
authors.forename: Peter S
authors.initials: PS
authors.lastname: Mortimer
authors.forename: A Michael
authors.initials: AM
authors.lastname: Peters
mesh_terms: D000328:Adult; D000368:Aged; D001132:Arm; D001943:Breast Neoplasms / Q000150:complications; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D007205:Indium Radioisotopes; D007279:Injections, Subcutaneous; D008196:Lymph / Q000502:physiology; D008209:Lymphedema / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D061305:Lymphoscintigraphy; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage; D015609:Organotechnetium Compounds / Q000008:administration & dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D012709:Serum Albumin / Q000008:administration & dosage; D000075462:Serum Albumin, Human; D013668:Technetium Tc 99m Aggregated Albumin / Q000008:administration & dosage
chemical_list: D003692:Delayed-Action Preparations; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012709:Serum Albumin; D013668:Technetium Tc 99m Aggregated Albumin; C035387:indium aggregated albumin; C079358:technetium TC 99m polyclonal IgG; D000075462:Serum Albumin, Human