Do [¹⁸F]FLT plasma levels and metabolism change with chemoradiation therapy?

Objectives To examine the intra- and inter-subject variability in [¹⁸F]FLT plasma levels and metabolic rate before and after chemoradiation therapy.

Methods Subjects (N= 12, 11M 1F, age range: 35 - 69 years) with Stage 3 or 4 head and neck cancer were imaged with [¹⁸F]FLT prior to and after one cycle of platinum-based chemotherapy and 10 Gy of a 70 Gy radiation therapy regimen. FLT (2.6 MBq/kg, max dose = 185 MBq) was administered by infusion over 2 minutes. Venous blood samples were drawn at 3, 5, 20 and 60 minutes post-start of infusion. Plasma aliquots were assayed for unchanged FLT using QMA Sep-pak separation methods. For comparison purposes, the plasma levels at each time point were normalized to 2.6 MBq/kg. The unmetabolized fractions were fit to a single exponential curve.

Results The metabolite-corrected, dose-normalized plasma concentrations pre- and mid-therapy, respectively, were, at 3 min, 14.9 ± 14.9 versus 14.5 ± 7.8; at 5 min, 6.7 ± 2.1 versus 6.9 ± 2.5; at 20 min, 2.5 ± 0.7 versus 2.8 ± 1.0; and at 60 min, 1.5 ± 0.6 versus 1.6 ± 0.5 kBq/cc (p = 0.92, 0.84, 0.37, 0.77, respectively). From 5 min onward, the inter-subject coefficient of variation in normalized plasma concentrations ranged from 27% to 37% and the mean intra-subject percent change ranged from 7.6% to 13.4%. The mean fitted metabolic rate constant was 0.0049 ± 0.0014 min^-1 versus 0.0051 ± 0.0015 min^-1 ,with 74.3% versus 74.2% unchanged FLT at 60 min (p = 0.74 and 0.99).

Conclusions Effective monitoring of the response to therapy with FLT requires that changes in uptake reflect changes in proliferation not the delivery or availability of the tracer imposed by alterations in systemic pharmacokinetics induced by therapy. There is no evidence of changes in intra-subject metabolite-corrected plasma concentration or inter-subject variability with short-term chemoradiation therapy, suggesting that blood sampling is not necessary for reliable quantitative FLT uptake comparisons during response to therapy assessments