SUVmax-based assessment of PET response shows a superior specificity to Deauville criteria for predicting recurrence in Hodgkin's lymphoma.

One of the limitations of 18FDG PET/CT for therapeutic evaluation in Hodgkin's Lymphoma is the relatively high rate of false positive uptake. SUVmax reduction (ΔSUVmax) and tumor/liver ratio (TLr) are promising tools for response assessment in lymphoma. We determined the optimal cutoff values for ΔSUVmax and TLr and compared them to Deauville score (DS) after two and four cycles chemotherapy (PET2 and PET4 respectively) and at the end of treatment PET (PETeot) on a cohort of 362 patients. TLr showed better diagnostic performances than DS for predicting 5-year progression-free survival (PFS), especially on early PET/CT assessments. Positive predictive values at PET2 for TLr, ΔSUVmax and DS were 51%, 34% and 31% respectively. On the multivariable analysis, significant predictive factors of PFS were TLr (at PET2, PET4 and PETeot) and ΔSUVmax (at PET4 and PETeot). DS was not significantly associated with PFS at any PET timing.

Impact of DOTA Conjugation on Pharmacokinetics and Immunoreactivity of [177Lu]Lu-1C1m-Fc, an Anti TEM-1 Fusion Protein Antibody in a TEM-1 Positive Tumor Mouse Model.

1C1m-Fc, an anti-tumor endothelial marker 1 (TEM-1) scFv-Fc fusion protein antibody, was previously successfully radiolabeled with 177Lu. TEM-1 specific tumor uptake was observed together with a non-saturation dependent liver uptake that could be related to the number of dodecane tetraacetic acid (DOTA) chelator per 1C1m-Fc. The objective of this study was to verify this hypothesis and to find the best DOTA per 1C1m-Fc ratio for theranostic applications. 1C1m-Fc was conjugated with six concentrations of DOTA. High-pressure liquid chromatography, mass spectrometry, immunoreactivity assessment, and biodistribution studies in mice bearing TEM-1 positive tumors were performed. A multi-compartment pharmacokinetic model was used to fit the data and a global pharmacokinetic model was developed to illustrate the effect of liver capture and immunoreactivity loss. Organ absorbed doses in mice were calculated from biodistribution results. A loss of immunoreactivity was observed with the highest DOTA per 1C1m-Fc ratio. Except for the spleen and bone, an increase of DOTA per 1C1m-Fc ratio resulted in an increase of liver uptake and absorbed dose and a decrease of uptake in tumor and other tissues. Pharmacokinetic models correlated these results. The number of DOTA per antibody played a determining role in tumor targeting. One DOTA per 1C1m-Fc gave the best pharmacokinetic behavior for a future translation of [177Lu]Lu-1C1m-Fc in patients.