Rowe JA, LeBlanc CJ.
Non-invasive techniques to evaluate bone marrow function are needed to optimize care of dogs with suspected or confirmed hematopoietic disorders. Positron Emission Tomography/Computed Tomography (PET/CT) using 18F-fluoro-l-deoxythymidine (18FLT), a PET tracer that physiologically concentrates in bone marrow and acts as a marker of cellular proliferation, offers a non-invasive imaging technique for whole-body assessment of marrow proliferation. Three (3) clinically normal, purpose-bred dogs were imaged using 18FLT for assessment of bone marrow proliferation at baseline and at 7 and 14 days post administration of a single dose of cyclophosphamide (225 mg/m2 PO) to nonselectively suppress hematopoiesis. PET/CT images were acquired with dogs under light general anesthesia following a minimum 12 hour fast. Regions of interest were drawn over sites of clinical relevance and increased tracer uptake, including common marrow sampling sites. Standardized uptake values were calculated utilizing dedicated analysis software. Bone marrow aspirates from both the proximal humerus and wing of the ilium were assessed within 24 hours of each imaging timepoint by cytology and flow cytometric cell cycle analysis for comparison with PET imaging findings. Cytologic analysis included estimation of overall cellularity with a 200-cell differential count discriminating cells as early erythroid, late erythroid, early granulocytic, late granulocytic, monocyte/ macrophage, lymphocyte, plasma cell, or other. CBCs were assessed daily after cyclophosphamide administration.
Despite development of profound circulating neutropenia (median neutrophil nadir 580 cells/uL, 8 days post-cyclophosphamide administration), no significant changes in overall marrow cellularity were detected. Statistically significant changes between sampling timepoints were detected in the granulocytic index (ratio of early to late granulocytic precursors) in the wing of the ilium aspirates (p=0.007), and flow cytometric cell cycle analysis was indicative of DNA insult at all sites sampled. Strong physio- logic 18FLT uptake remained present in axial and proximal appendicular marrow sites. Changes over time in SUVmax were significant (p=0.003) in proximal humerus but not wing of ilium sites. Reports in humans with myeloproliferative diseases demonstrate utility of 18FLT-PET in characterizing such diseases. Changes observed in bone marrow samples in this study preclude correlation between 18FLT signal and marrow function, likely due to cyclophosphamide-induced cell cycle arrest rather than cytotoxicity. Future studies using site-specific marrow ablative techniques are planned to produce more conspicuous marrow hypocellularity.