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Quantification of Lymphatic Function for Investigation of Lymphedema: Depot Clearance and Rate of Appearance of Soluble Macromolecules in Blood

¹ Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge, United Kingdom
² Department of Nuclear Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom
³ Department of Medicine, St. George’s Hospital Medical School and The Royal Marsden National Health Service Trust, London, United Kingdom

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 ¹¹¹In on one side and with ^99mTc 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: ^99mTc-HSA cleared from the depot consistently faster than ¹¹¹In-HSA (P = 0.001). The proportions of radionuclide remaining bound to protein in venous blood were higher for ^99mTc than for ¹¹¹In. 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. Conclusion: 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. ^99mTc-HSA cleared faster than ¹¹¹In-HSA and yet displayed better in vivo labeling stability. We conclude that ¹¹¹In 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.

Key Words: lymphatic function • lymphedema • depot clearance

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