FLT Imaging Reveals Kinetics and Biology of Engraftment after Myeloablative HSCT

Bone marrow failure is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT) due to complications associated with prolonged neutropenia. Using the positron emission tomography (PET) imaging probe, 3’-deoxy-3 ¹⁸F-fluorothymidine (¹⁸FLT), we illustrate HSC homing very early after myeloablative HSCT in adults in vivo. In our prospective trial, NCT01338987, we imaged 14 patients undergoing myeloablative transplantation with Cytoxan and total body irradiation and evaluated corresponding uptake of radiotracer ¹⁸FLT in osseous structures throughout the bone marrow compartment following full myeloblation, early engraftment, and hematopoietic reconstitution. ¹⁸FLT was safe and did not delay engraftment. Objective increases in ¹⁸FLT uptake measured by standardized uptake value (SUV) revealed evidence of stem cell homing to medullary bone marrow sites within 5 days of donor cell infusion. In patients without relapse (n=11), mean thoracic spine SUV was greater among patients with rapid (<21 days) as compared to slow engraftment (≥21 days). Using SUV, we could differentiate full ablation (SUV of 0.65) from early engraftment at day +5-6 (SUV 1.1, p <0.05). ¹⁸FLTsignal increases revealed a consistent pattern of marrow recovery that recapitulated fetal ontogeny, claiming sites of hematopoiesis that are normally dormant in adults. These findings were substantiated with in vitro cellular recovery data. ¹⁸FLT SUV could also predict marrow recovery after secondary graft failure without additional HSC infusion. In summary, our data show that ¹⁸FLT reveals homing, kinetics, and biology of hematopoietic engraftment in adults in vivo.¹⁸FLT could predict engraftment very early after HSCT and could be of value to predict primary or secondary graft failure in high risk populations, such as recipients of cord blood transplantation or haplo-identical transplantation.