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

• Published in: European journal of nuclear medicine and molecular imaging 2011-07, Vol.38 (7), p.1270-1280
• Main Authors: Walrand, Stephan, Barone, Raffaella, Pauwels, Stanislas, Jamar, François
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological Transport; Blood Platelets - cytology; Blood Platelets - radiation effects; Bone Marrow - diagnostic imaging; Bone Marrow - metabolism; Bone Marrow - radiation effects; Cardiology; Chelating Agents - chemistry; Female; Humans; Imaging; Male; Medicine; Medicine & Public Health; Middle Aged; Nuclear Medicine; Octreotide - adverse effects; Octreotide - analogs & derivatives; Octreotide - chemistry; Octreotide - metabolism; Octreotide - therapeutic use; Oncology; Original Article; Orthopedics; Pentetic Acid - adverse effects; Pentetic Acid - analogs & derivatives; Pentetic Acid - chemistry; Pentetic Acid - metabolism; Pentetic Acid - therapeutic use; Platelet Count; Positron-Emission Tomography; Radiation Dosage; Radiography; Radiology; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Whole-Body Irradiation - adverse effects
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-011-1744-x

Purpose The aim of this study was to retrospectively evaluate whether the red marrow (RM) takes up 111 In-diethylenetriaminepentaacetic acid (DTPA)- D -Phe 1 -octreotide and 86 Y-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 111 In single photon emission computed tomography (SPECT) and 86 Y 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 111 In-DTPA- D -Phe 1 -octreotide and 90 Y-DOTATOC in plasma. Results The correlation between the uptake of both tracers was excellent ( R  = 0.80), indicating that RM uptake of 86 Y-DOTATOC reflects a real physiological process and not reconstruction artefacts. The kinetics of 86 Y-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.