Abstract
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Objectives To assess the pharmacokinetics and to establish the safety profile by applying common toxicity criteria using dose escalation protocol.
Methods 15 patients(12 M, 3 F) with painful skeletal metastatic disease from prostate or breast ca were enrolled. Karnofsky status was >60 in all patients with normal liver, renal & hematologic lab tests. The 177Lu-EDTMP activity was determined by prospective dosimetry using a 74 MBq of 177Lu-EDTMP to deliver a desired increasing radiation absorbed dose to the bone marrow(150, 200, 250, 300, 350 cGy). Each group had 3 pts. Mean injected activity was 1870 MBq. Blood and urinary clearances were determined by sequential blood & urine sample collection. 177Lu-EDTMP images were acquired at 0.5, 4, 8, 24, 48 hr, 7 & 14 days.Bone uptake was calculated by ROI technique Blood chemistry including full blood cell counts was assessed at 2, 4, 6, 8 wks.
Results Blood clearance of 177Lu-EDTMP was rapid within first 30 mins, a negligible fraction of the injected activity remained in the blood at 24 hr. Urinary excretion was 22.4±13.8% at 4 hr & 30.7±2.85% at 24hr. Bone uptake was 69±12.6% at 4 hr, 72±11% at 24 hr, & 72.4±12.2% at 48 hr. No dose limiting toxicity was observed by the NCI CTC criteria. None of the patients had hematological toxicity beyond grade 2. Only 3 patients had grade 2, and 3 patients had grade1 toxicity. 2 pts had a drop in leucocytes <3500/mm3, one had a drop platelets below 100,000/mm3 and 3 patients had Hb level <9 g/dL. Recovery was complete within 8 wks without intervention. Blood chemistry and urine analysis was unremarkable,
Conclusions 177Lu-EDTMP shows adequate bone uptake, rapid urinary excretion & prolonged retention in the bone. Hematologic toxicity was mild & transient. All these characteristics along with its optimum physical and chemical properties render 177Lu-EDTMP a promising therapeutic agent for pain palliation of skeletal metastatic.
Research Support IAE