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Local Vascular Access of Radioprotein Injected Subcutaneously in Healthy Subjects and Patients with Breast Cancer–Related Lymphedema

¹ Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge, United Kingdom
² Department of Nuclear Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom
³ Department of Physiological Medicine, St George’s Hospital Medical School, London, United Kingdom

The aim of the study was to use dual-isotope lymphoscintigraphy in healthy volunteers and women with breast cancer–related lymphedema (BCRL) to detect and quantify transport of radiolabeled protein from a subcutaneous injection depot to local blood vessels as a potential mechanism of protection against edema resulting from treatment to the axilla. Methods: A total of 29 subjects and 18 women with a history of BCRL received bilateral subcutaneous injections of human IgG (HIgG) in the second dorsal web space of each hand, ^99mTc-HIgG on one side and ¹¹¹In-HIgG on the other. In 8 further healthy subjects, epinephrine was administered with the labeled HIgG. Radioactivity at each depot was measured at regular intervals for a total of 3 h using a collimated sodium iodide scintillation detector, and radioactivity in venous blood sampled from both arms was measured using an automatic sample counter. Ipsilateral blood time–concentration curves were corrected for recirculating activity by subtraction of the simultaneous contralateral concentration, to define the component of ipsilateral blood resulting from local vascular access of radioprotein. Accumulation of activity in blood was expressed in relation to injected activity and activity that had left the depot and was calculated as a function of time—in systemic blood, by multiplying contralateral concentrations by an estimate of the subject’s blood volume, and in ipsilateral blood, by using indicator dilution theory and an assumed forearm blood flow of 20 mL/min. Results: ^99mTc-HIgG and ¹¹¹In-HIgG behave almost identically with respect to depot clearance and accumulation in contralateral venous blood, with or without epinephrine, which reduced both depot clearance and blood accumulation rate. Moreover, a side-to-side correlation with respect to contralateral accumulation was present in healthy subjects, was not abolished by epinephrine, and was maintained in the face of asymmetric accumulation in BCRL. Contralateral accumulation of radioprotein was reduced in BCRL after injection into the affected side only when the hand was involved. In contrast to contralateral sampling, ipsilateral time–concentration and accumulation profiles were consistent with instability of ¹¹¹In-HIgG and rapid local vascular access of small amounts of protein-free ¹¹¹In. Experiments based on precipitation of protein with trichloroacetic acid confirmed relatively high levels of unbound ipsilateral ¹¹¹In, especially in samples obtained early after injection. Substantial accumulation of protein-bound ^99mTc was observed in ipsilateral blood, with a time course similar to that of contralateral accumulation. Positive correlation between ipsilateral and contralateral blood ^99mTc activity was observed at all time points, often significantly, in contrast to ¹¹¹In, for which it was negative at all time points. Ipsilateral accumulation of ^99mTc adjusted for activity that had left the depot was unchanged with respect to the affected arm in BCRL patients. Conclusion: Whereas ¹¹¹In-HIgG and ^99mTc-HigG are interchangeable for measurement of depot clearance and contralateral venous accumulation rates, ipsilateral sampling is much more sensitive to protein-free radionuclide and detects significant differences resulting from some instability of ¹¹¹In-HIgG. On the basis of ^99mTc data, there appears to be substantial local vascular access of radioprotein within the arm, both in healthy subjects and in patients with BCRL, through either lymphaticovenous communications or direct transendothelial transport.

Key Words: lymphoscintigraphy • breast cancer—related lymphedema • human IgG

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