99mTc-interleukin-2 scintigraphy in normal subjects and in patients with autoimmune thyroid diseases: a feasibility study

Abstract

Purpose Radiolabelled interleukin-2 is a radiopharmaceutical used for the study of chronic inflammatory processes. 123 I-labelled interleukin-2 has successfully been used in a large number of patients affected by several immunemediated diseases. 123I, however, is expensive and not readily available. We have, therefore, developed a method for labelling interleukin-2 with 99m Tc to high specific activity based on the use of an N 3 S bifunctional chelating agent. In this paper, we describe the results obtained with 99m Tc-interleukin-2 in a series of eight normal subjects and of 12 patients with autoimmune thyroid diseases. Methods Biodistribution, pharmacokinetics, haematological and systemic toxicity, radiation absorbed dose and in vivo targeting were studied.Results Results showed rapid plasma clearance of 99m Tcinterleukin-2 with retention mainly in the kidneys. Biodistribution and kinetics were similar to that observed for 123 I-interleukin-2. No acute systemic toxicity was found; a small decrease in peripheral blood lymphocytes was observed in the first hours only in patients, but it was mild and transient. Tc-interleukin-2 accumulated, to varying extents, in the thyroid of all patients affected by autoimmune thyroid diseases but not in the thyroid of normal subjects. The effective dose equivalent of a diagnostic activity of 99m Tc-interleukin-2 (185 MBq) was 1.35 mSv. No correlation was observed between thyroid autoantibodies and uptake of 99m Tc-interleukin-2. Conclusions The use of 99m Tc-interleukin-2 is safe and simple; the favourable dosimetry and biodistribution and the rapid clearance make it potentially useful for the study of chronic inflammatory diseases such as autoimmune thyroid disease.

Non-invasive visualization of tumor infiltrating lymphocytes in patients with metastatic melanoma undergoing immune checkpoint inhibitor therapy: a pilot study

“…Succinimidyl-6-hydrazinopyridine-3-carboxylate (HYNIC-NHS) was conjugated to the commercially obtained IL2 as previously described [ 9 – 10 ]. Briefly, HYNIC-IL2 (100 μg) was incubated with tricine, 99m TcO - (370–740 MBq) and SnCl 2 for 10 min at room temperature.…”

“…Due to concerns about potential adverse effects on the thyroid from a radioactive iodine based radiopharmaceutical, the investigators next employed a 99mTechnicium labeled interleukin-2 ( 99m Tc-IL2). We have demonstrated that this approach was able to visualize lymphocyte infiltration in the bowel (Crohn's disease) as well as in the thyroid (autoimmune thyroiditis) [ 7 – 9 ]. Next, we examined 21 early stage melanoma primary skin lesions prior to surgical resection with 99m Tc-IL2 imaging for the presence of TIL and corresponding 99m Tc-IL2 uptake by histologic evaluation of the surgical specimen.…”

The molecular imaging approach to image infections and inflammation by nuclear medicine techniques

“…Another study in asymptomatic Sjogren syndrome patients, salivary gland scintigraphy by 99m Tc-IL-2, showed clear pathological uptake in patients with biopsy-proven infiltrated glands [118].…”

Immuno-Imaging to Predict Treatment Response in Infection, Inflammation and Oncology

“…Studies using radiolabelled IL2 started in the 1980s and first radioisotopes used were 125 I and 35 S for in vitro and animal studies [134,135,136]. Radiolabelled IL2 was extensively studied in animal models and patients with diabetes [137,138,139,140], in order to research T lymphocyte infiltrates in rats’ renal allografts [141], in Crohn’s and coeliac disease patients [142,143], in other autoimmune disorders [144,145,146] and for imaging of vulnerable atherosclerotic plaques [147,148].…”