ABSTRACT
Recent advancements in the field of immune-oncology have led to a significant increase in life expectancy of patients with diverse forms of cancer, such as hematologic malignancies, melanoma and lung cancer. Unfortunately, these encouraging results are not observed in the majority of patients, who remain unresponsive and/or encounter adverse events. Currently, researchers are collecting more insight into the cellular and molecular mechanisms that underlie these variable responses. As an example, the human lymphocyte activation gene-3 (huLAG-3), an inhibitory immune checkpoint receptor, is increasingly studied as a therapeutic target in immune-oncology. Noninvasive molecular imaging of the immune checkpoint programmed death protein-1 (PD-1) or its ligand PD-L1 has shown its value as a strategy to guide and monitor PD-1/PD-L1-targeted immune checkpoint therapy. Yet, radiotracers that allow dynamic, whole body imaging of huLAG-3 expression are not yet described. We here developed single-domain antibodies (sdAbs) that bind huLAG-3 and showed that these sdAbs can image huLAG-3 in tumors, therefore representing promising tools for further development into clinically applicable radiotracers.
ABSTRACT
A prospective study was made of 125 ureteric stones in order to detect factors which would predict the successful outcome of conservative treatment. The factors studied were the duration of pain prior to presentation, pyuria, haematuria, surface regularity of the stone and the degree of obstruction as seen radiologically. In stones less than or equal to 10 mm in size, conservative treatment was successful when the duration of pain was less than 30 days (39/45), when there was no significant pyuria (53/82), when the stones had an irregular surface (44/65) and when obstruction was only partial (55/88). Since most of these factors were interactive, further statistical analysis showed that duration of pain was the only significant factor in predicting the outcome of conservative treatment. In stones greater than 10 mm in size these factors had no predictive value and only 2/23 were passed spontaneously on conservative treatment.
