Peptide radionuclide receptor therapy (PRRT) with Lu-177-DOTA, Tyr3-octreotate (LuTATE): Risk factors, radiation dose and BED, impact on long-term renal toxicity

Objectives Peptide receptor radionuclide therapy (PRRT) may induce renal insufficiency; a biologic equivalent dose (BED) of 35 Gy was postulated as safe limit for Y-90 labeled compounds. Hypertension (HT) and diabetes (DM) are regarded as risk factors. We evaluated renal toxicity after PRRT with LuTATE in patients (pts) who had evaluable dosimetry and long follow-up.

Methods Renal function (creatinine clearance; CLR) was monitored in 38 pts (19M, 19F, age 57.7 ± 11.7 yr) after PRRT with LuTATE (600-800 mCi in 3-8 cycles), all with renoprotective amino acids. 11/38 pts were later retreated with (mostly) 2 x 200 mCi. All patients had scintigraphic dosimetry and at least 18 months follow-up (median 4.5yr, range 1.7 - 9.1). 7 pts had HT, 8 had DM of whom 2 had HT + DM. The median renal BED from the initial PRRT was 22.4 Gy [range 10.5 - 33.3]. After retreatment (n=11, follow-up 0.2 - 3.8 yr) the median total BED was 39.1 Gy [range 15.8 - 41.7].

Results For individual pts, CLR loss continued during follow-up. The median CLR loss was mild at 3.6%/yr. We found no clearly increased loss after retreatment. 4 pts had CLR loss >10%/yr (M, 60yr, HT + DM, 24.4Gy, CLR -37%/yr / M, 49yr, HT, preterminal illness, 15.2Gy, CLR -17%/yr, / F, 48yr, preterminal illness, 23.3Gy, CLR -16%/yr / M, 78yr, HT + DM, 16.0Gy, CLR -11%/yr). Over the range of BED's given, we found no significant correlation between BED and CLR loss.

Conclusions PRRT with LuTATE, in 4 (+ 2 extra) cycles of 200 mCi, does not lead to important long-term renal toxicity. The effect of BED on CLR loss appeared less profound than other factors like combined HT + DM or general illness in this study