Date: 12 Feb 2011

Experimental facts supporting a red marrow uptake due to radiometal transchelation in 90Y-DOTATOC therapy and relationship to the decrease of platelet counts

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Abstract

Purpose

The aim of this study was to retrospectively evaluate whether the red marrow (RM) takes up 111In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe1-octreotide and 86Y-DOTATOC and to assess the correlation between the RM absorbed doses and platelet count reduction as a biological dose estimate.

Methods

Data from 12 patients who underwent at 24 h p.i. high statistics 111In single photon emission computed tomography (SPECT) and 86Y positron emission tomography (PET) acquisitions of the chest were analysed. Uptake was measured on >7 cm spine length and converted to total RM uptake using standard RM distribution in man. RM absorbed doses were calculated assuming specific RM uptake and using the plasma and remainder of the body models. RM doses were correlated with the platelet count reduction at 4 weeks. In vitro experiments explored the metabolism of 111In-DTPA-D-Phe1-octreotide and 90Y-DOTATOC in plasma.

Results

The correlation between the uptake of both tracers was excellent (R = 0.80), indicating that RM uptake of 86Y-DOTATOC reflects a real physiological process and not reconstruction artefacts. The kinetics of 86Y-DOTATOC RM activity was different than that in blood and tumours, with no activity at 4 h p.i. indicating that the uptake is not somatostatin receptor dependent. In vitro experiments showed a transchelation of both radiometals to free transferrin that could explain the RM uptake. In patients without chemotherapy and with a normal platelet count recovery, a good correlation (R = 0.96) was found between the RM doses and the platelet count reduction at the nadir.

Conclusion

These experimental facts support the existence of a true RM uptake likely related to transchelation of the radiometal to transferrin. RM uptake correlates well with the observed acute RM toxicity.