[(67)Ga]SB3 showed excellent pharmacokinetics in PC-3 tumor-bearing mice, while [(68)Ga]SB3 PET/CT visualized lesions in about 50 % of patients with advanced and metastasized prostate and breast cancer. We expect imaging with [(68)Ga]SB3 to be superior in patients with primary breast or prostate cancer.
PurposeIn peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted from 131I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients treated with PRRT with 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE). Also, absorbed BM dose estimates were evaluated and compared with the accepted 2 Gy dose limit.MethodsThe incidence and duration of grade 3 or 4 haematological toxicity (according to CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit (gigabecquerels) of administered radioactivity was calculated and the correlations between doses to the BM and haematological risk factors were determined.ResultsHaematological toxicity (grade 3/4) occurred in 34 (11 %) of 320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood transfusions were required. Risk factors significantly associated with haematological toxicity were: poor renal function, white blood cell (WBC) count <4.0 × 109/l, age over 70 years, extensive tumour mass and high tumour uptake on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per administered activity in 23 evaluable patients was 67 ± 7 mGy/GBq, resulting in a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq 177Lu-DOTATATE. Significant correlations between (cumulative) BM dose and platelet and WBC counts were found in a selected group of patients.ConclusionThe incidence of subacute haematological toxicity after PRRT with 177Lu-DOTATATE is acceptable (11 %). Patients with impaired renal function, low WBC count, extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age are more likely to develop grade 3/4 haematological toxicity. The BM dose limit of 2 Gy, adopted from 131I, seems not to be valid for PRRT with 177Lu-DOTATATE.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-015-3193-4) contains supplementary material, which is available to authorized users.
PurposeAfter peptide receptor radionuclide therapy (PRRT), renal toxicity may occur, particular in PRRT with 90Y-labelled somatostatin analogues. Risk factors have been identified for increased probability of developing renal toxicity after PRRT, including hypertension, diabetes and age. We investigated the renal function over time, the incidence of nephrotoxicity and associated risk factors in patients treated with PRRT with [177Lu-DOTA0,Tyr3]-Octreotate (177Lu-Octreotate). Also, radiation dose to the kidneys was evaluated and compared with the accepted dose limits in external beam radiotherapy and PRRT with 90Y-radiolabelled somatostatin analogues.MethodsThe annual decrease in creatinine clearance (CLR) was determined in 209 Dutch patients and the incidence of grade 3 or 4 renal toxicity (according to CTCAE v4.03) was evaluated in 323 patients. Risk factors were analysed using a nonlinear mixed effects regression model. Also, radiation doses to the kidneys were calculated and their association with high annual decrease in renal function were analysed.ResultsOf the 323 patients, 3 (1 %) developed (subacute) renal toxicity grade 2 (increase in serum creatinine >1.5 – 3.0 times baseline or upper limit of normal). No subacute grade 3 or 4 nephrotoxicity was observed. The estimated average baseline CLR (± SD) was 108 ± 5 ml/min and the estimated average annual decrease in CLR (± SD) was 3.4 ± 0.4 %. None of the risk factors (hypertension, diabetes, high cumulative injected activity, radiation dose to the kidneys and CTCAE grade) at baseline had a significant effect on renal function over time. The mean absorbed kidney dose in 228 patients was 20.1 ± 4.9 Gy.ConclusionNephrotoxicity in patients treated with 177Lu-octreotate was low. No (sub)acute grade 3 or 4 renal toxicity occurred and none of the patients had an annual decrease in renal function of >20 %. No risk factors for renal toxicity could be identified. Our data support the idea that the radiation dose threshold, adopted from external beam radiotherapy and PRRT with 90Y-labelled somatostatin analogues, does not seem valid for PRRT with 177Lu-octreotate.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-016-3382-9) contains supplementary material, which is available to authorized users.
Peptide Receptor Radionuclide Therapy (PRRT) may induce long-term toxicity to the bone marrow (BM). The aim of this study was to analyze persistent dysfunction of the hematopoietic system after PRRT with 177 Lu-DOTATATE in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods:The incidence and course of persistent hematological dysfunction (PHD) was analyzed Results:We identified 11 (3.7%) out of 274 GEP-NET patients with PHD following treatment with No risk factors were identified for developing PHD in GEP-NET patients.
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