In vivo assessment of anti-tuberculous drug delivery in patients with tuberculous lymphadenitis by ^99mTechnetium ethambutol scintigraphy

India has the highest number TB cases worldwide and a robust tuberculosis control program which involves treatment with anti-tubercular drugs for 6-24 months. It is difficult to predict non-responders at the time of initiating therapy. In this pilot study, we aim to assess the ^99mTechnetium (Tc) Ethambutol (EMB) uptake in known tuberculous lesions with a theranostic intent. 7 patients with known tuberculous lymphadenitis were recruited in the study and were injected 10-20 mCi of ^99mTc-labelled antibiotic (Ethambutol) and serial anterior and posterior whole-body scans on a dual head gamma camera were acquired. The scans were acquired as 15 min dynamic and 1 h, 2 h, 4 h and 8 h. SPECT/CT was acquired between 1-2 hours. The uptake detected in the lesions was assessed visually and compared to the uptake in liver. 7 patients with known tuberculous lymphadenitis were assessed out of which 3 were females and 4 were males. The age range was 20-67 years with a median age of 26 years. 2 patients had only cervical lymphadenopathy, 1 patient had cervical as well as axillary lymphadenopathy and 1 patient had cervical, mediastinal and abdominal lymphadenopathy. 2 patients had only mediastinal lymphadenopathy. 1 patient had mediastinal and abdominal lymphadenopathy. In addition to the known nodal sites, 3 patients also had involvement of lungs, intestines and soft tissue. Among these 7 patients, we could identify regional lymphadenopathy in 5 patients. In all 5 patients we could identify 1 regional lymphadenopathy each (4 cervical and 1 abdominal). The ratio of the maximum tracer uptake in the lesion to the maximum tracer uptake was calculated and was in the range of 0.6 to 1.1 with the median being 0.8. Two patients with known lymphadenopathy and but negative on ^99mTechnetium scintigraphy showed mild tracer uptake in lungs and in a pre-sternal abscess respectively with corresponding changes on CT. 1 patient with abdominal lymphadenopathy and intestinal involvement which were both noted on the initial ^99mTechnetium scintigraphy underwent another scan after 2 months of anti-tuberculous treatment and showed uptake in the previously noted lesions. ^99mTechnetium EMB scintigraphy may be able to help in the assessment of in vivo drug delivery to the intended target sites (viable mycobacteria) in patients with tuberculosis. Since, inhibition of drug uptake is one of the resistance mechanisms displayed by M. tuberculosis the above findings may have theranostic implications in the future. (author)