Pharmacokinetics and dosimetry of the bone-seeking agent 177Lu-EDTMP in patients with metastatic prostate cancer

Objectives 177Lu-EDTMP has been proposed as an alternative to 153Sm-EDTMP for palliation of metastatic bone pain. Physical half-life of 177Lu (6.71 days) makes it logistically convenient. Its relatively low energy β-particles (0.497 MeV) may entail low bone marrow toxicity, γ emission suitable for γ-camera imaging allows for dosimetric measurements. Preclinical studies in mice, rats, rabbits and dogs showed excellent biodistribution patterns; peak bone uptake of 41% ID at 1-3 hr. In dogs, mild hematologic toxicity (reduced platelet count 1 week p.i.) accured only in the highest activity group (37MBq/kg bw). We report the results of a pilot 177Lu-EDTMP pharmacokinetic and dosimetric study in humans.

Methods Six pts with bone-metastatic or non-metastatic prostate cancer received a tracer amount of 177Lu-EDTMP (185 MBq). Pharmacokinetics up to 6 days p.i. was based on conjugated-view whole-body γ-camera imaging and blood sampling, while urine collection was continued until 48 hr p.i.; OLINDA was used for dosimetric estimates.

Results Blood clearance was biexponential, average T1/2 values were 0.33 and 11h, respectively. Bone uptake peaked at 1-2 hr, mean residence times were 97 and 132 hr in the skeleton and whole body, respectively. Plateau in urine excretion was reached between 8-24 hr at an average 38% ID, being highest with low metastatic burden (58% ID) and lowest with high metastatic burden (24% ID). Estimated absorbed doses were 5.41, 1.53 and 0.8 mSv/MBq for osteogenic cells, urinary bladder wall and red bone marrow, respectively.

Conclusions 177Lu-EDTMP has excellent pharmacokinetic and dosimetric properties. Assuming 200 cGy as the maximum tolerated dose to the red bone marrow, maximum activity to be administered to patients ranges between 30 and 52 MBq/kg bw.

Research Support IAEA, CRP#E1303