Renal function affects absorbed dose to the kidneys and haematological toxicity during 177Lu-DOTATATE treatment

Abstract

PurposePeptide receptor radionuclide therapy (PRRT) has become an important treatment option in the management of advanced neuroendocrine tumours. Long-lasting responses are reported for a majority of treated patients, with good tolerability and a favourable impact on quality of life. The treatment is usually limited by the cumulative absorbed dose to the kidneys, where the radiopharmaceutical is reabsorbed and retained, or by evident haematological toxicity. The aim of this study was to evaluate how renal function affects (1) absorbed dose to the kidneys, and (2) the development of haematological toxicity during PRRT treatment.MethodsThe study included 51 patients with an advanced neuroendocrine tumour who received 177Lu-DOTATATE treatment during 2006 – 2011 at Sahlgrenska University Hospital in Gothenburg. An average activity of 7.5 GBq (3.5 – 8.2 GBq) was given at intervals of 6 – 8 weeks on one to five occasions. Patient baseline characteristics according to renal and bone marrow function, tumour burden and medical history including prior treatment were recorded. Renal and bone marrow function were then monitored during treatment. Renal dosimetry was performed according to the conjugate view method, and the residence time for the radiopharmaceutical in the whole body was calculated.ResultsA significant correlation between inferior renal function before treatment and higher received renal absorbed dose per administered activity was found (p < 0.01). Patients with inferior renal function also experienced a higher grade of haematological toxicity during treatment (p = 0.01). The residence time of 177Lu in the whole body (range 0.89 – 3.0 days) was correlated with grade of haematological toxicity (p = 0.04) but not with renal absorbed dose (p = 0.53).ConclusionPatients with inferior renal function were exposed to higher renal absorbed dose per administered activity and developed a higher grade of haematological toxicity during 177Lu-DOTATATE treatment. The study confirms the tolerability of PRRT in patients with an advanced neuroendocrine tumour but indicates that patients with inferior renal function are at risk of being exposed to higher absorbed doses to normal tissue on treatment.

Pre-therapeutic dosimetry of normal organs and tissues of 177Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer

“…Accordingly it showed substantial variance among patients ranging from 34.3 to 95.7 GBq, and highest radiation doses were observed in patients who had extensive bone metastases and mechanical obstruction due to extensive disease in the prostate gland (patients 2, 3, and 5). It has been shown that total body residence time increases in patients with decreased renal function and high tumor burden and correlated with bone marrow toxicity during 177 Lu-DOTATATE therapy [18][19][20]. In accordance with these results, we observed the longest residence time in patients who had extensive bone metastases and decreased urinary excretion function due to mechanical urinary obstruction (patients 2, 3, and 5).…”

“…This amount of activity is perfectly correlated with the radioactivity amount found for 177 Lu-DOTATATE treatment, which was found to be 33.3 GBq [21]. Conditions that may affect renal function and increase radiation-absorbed dose to the kidneys have been suggested to be older age, prior chemotherapy, and accompanying diseases such as diabetes and hypertension [19,20,22]. Accordingly, the amount of radiation-absorbed dose given to the kidneys showed a considerable difference ranging from 13.8 to 44.9 GBq due to individual differences in disease state and renal function between patients.…”

“…The calculated bone marrow radiation-absorbed doses with 177 Lu-DOTATATE have been reported to range from 0.03 to 0.07 mg/MBq [16][17][18]. The factors that may affect the radiation dose to bone marrow are impairment of renal function or mechanical obstruction of the urinary tract, tumor load, and presence of bone metastases [18,19]. Accordingly it showed substantial variance among patients ranging from 34.3 to 95.7 GBq, and highest radiation doses were observed in patients who had extensive bone metastases and mechanical obstruction due to extensive disease in the prostate gland (patients 2, 3, and 5).…”

The impact of 177Lu-octreotide therapy on 99mTc-MAG3 clearance is not predictive for late nephropathy

“…A similar correlation has recently been found by Svensson et al . who reported that renal absorbed doses appeared to be higher in patients with baseline impaired renal function [18]. Interestingly, loss of eGFR in the follow-up was not associated with kidney uptake during therapy.…”

“…Renal irradiation from PRRT is most likely to be caused by uptake of radiolabeled somatostatin analogues in the proximal tubules where the radio-peptide is reabsorbed by the megalin receptor and subsequently retained in the interstitium [12, 15]. Hence, the tubular extraction might be a superior indicator for early stages of kidney affection by PRRT [12, 13]. …”