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²¹³Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience.

Kratochwil C, Giesel FL, Bruchertseifer F, Mier W, Apostolidis C, Boll R, Murphy K, Haberkorn U, Morgenstern A - Eur. J. Nucl. Med. Mol. Imaging (2014)

Bottom Line: Chronic kidney toxicity was moderate.Acute haematotoxicity was even less pronounced than with the preceding beta therapies.TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120, Heidelberg, Germany, clemens.kratochwil@t-online.de.

ABSTRACT

Purpose: Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as (90)Y/(177)Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with (213)Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters.

Methods: Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with (90)Y/(177)Lu-DOTATOC were treated with an intraarterial infusion of (213)Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of (213)Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and (68)Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients.

Results: The biodistribution of (213)Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies.

Conclusion: TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses.

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Related in: MedlinePlus

Patient 3 with the acute danger of occlusion of both the liver veins and the lower caval vein due to a large lesion in the upper central liver (a, MR image) which was addressed by locoregional DOTATOC therapy administered into the proper hepatic artery (b, digital subtraction angiogram). Intense 68Ga-DOTATOC uptake and uptake of contrast medium for CT was present in the initial staging (c, fused PET/CT image). Only PET-negative, morphologically cystic residuals were found 6 months after therapy (d, fused PET/CT image)
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Fig4: Patient 3 with the acute danger of occlusion of both the liver veins and the lower caval vein due to a large lesion in the upper central liver (a, MR image) which was addressed by locoregional DOTATOC therapy administered into the proper hepatic artery (b, digital subtraction angiogram). Intense 68Ga-DOTATOC uptake and uptake of contrast medium for CT was present in the initial staging (c, fused PET/CT image). Only PET-negative, morphologically cystic residuals were found 6 months after therapy (d, fused PET/CT image)

Mentions: Patient 3 was a 40-year-old woman with a pulmonary carcinoid with hepatic metastases. Pathology of the resected pulmonary specimen revealed moderate to undifferentiated grade II/III disease (Ki-67 30 %). Under carboplatin/etoposide therapy the tumour progressed in the liver. Subsequent locoregional infusion of 90Y-DOTATOC also failed to halt progression. Imaging revealed the acute danger of occlusion of the liver vein and the lower caval vein. Therefore, this patient received, 19.3 GBq 213Bi-DOTATOC divided into five cycles administered through a hepatic artery catheter. A partial response was observed in the liver and the response had been maintained for 34 months at the time of this report (Fig. 4). Patient 4 was referred to our department with hepatic encephalopathy due to extensive liver metastases. After intraarterial administration of 213Bi-DOTATOC to a cumulative dose of 20.8 GBq, the patient was stable for 1 year without a further hepatic event and then extrahepatic progression was diagnosed. Patient 5 failed to respond to conventional somatostatin analogue therapy but demonstrated a partial response in the liver and pancreatic primary tumour to the first three cycles of 90Y-DOTATOC, but then became refractory. Liver metastases (proper hepatic artery) and the primary tumour (gastroduodenal artery) were simultaneously accessible by 213Bi-DOTATOC injection into the common hepatic artery. After receiving 13.3 GBq 213Bi-DOTATOC intraarterially into the shared feeder, complete responses were observed in the liver and the primary, which had been maintained for 28 months at the time of this report (Fig. 5).Fig. 4


²¹³Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience.

Kratochwil C, Giesel FL, Bruchertseifer F, Mier W, Apostolidis C, Boll R, Murphy K, Haberkorn U, Morgenstern A - Eur. J. Nucl. Med. Mol. Imaging (2014)

Patient 3 with the acute danger of occlusion of both the liver veins and the lower caval vein due to a large lesion in the upper central liver (a, MR image) which was addressed by locoregional DOTATOC therapy administered into the proper hepatic artery (b, digital subtraction angiogram). Intense 68Ga-DOTATOC uptake and uptake of contrast medium for CT was present in the initial staging (c, fused PET/CT image). Only PET-negative, morphologically cystic residuals were found 6 months after therapy (d, fused PET/CT image)
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4525192&req=5

Fig4: Patient 3 with the acute danger of occlusion of both the liver veins and the lower caval vein due to a large lesion in the upper central liver (a, MR image) which was addressed by locoregional DOTATOC therapy administered into the proper hepatic artery (b, digital subtraction angiogram). Intense 68Ga-DOTATOC uptake and uptake of contrast medium for CT was present in the initial staging (c, fused PET/CT image). Only PET-negative, morphologically cystic residuals were found 6 months after therapy (d, fused PET/CT image)
Mentions: Patient 3 was a 40-year-old woman with a pulmonary carcinoid with hepatic metastases. Pathology of the resected pulmonary specimen revealed moderate to undifferentiated grade II/III disease (Ki-67 30 %). Under carboplatin/etoposide therapy the tumour progressed in the liver. Subsequent locoregional infusion of 90Y-DOTATOC also failed to halt progression. Imaging revealed the acute danger of occlusion of the liver vein and the lower caval vein. Therefore, this patient received, 19.3 GBq 213Bi-DOTATOC divided into five cycles administered through a hepatic artery catheter. A partial response was observed in the liver and the response had been maintained for 34 months at the time of this report (Fig. 4). Patient 4 was referred to our department with hepatic encephalopathy due to extensive liver metastases. After intraarterial administration of 213Bi-DOTATOC to a cumulative dose of 20.8 GBq, the patient was stable for 1 year without a further hepatic event and then extrahepatic progression was diagnosed. Patient 5 failed to respond to conventional somatostatin analogue therapy but demonstrated a partial response in the liver and pancreatic primary tumour to the first three cycles of 90Y-DOTATOC, but then became refractory. Liver metastases (proper hepatic artery) and the primary tumour (gastroduodenal artery) were simultaneously accessible by 213Bi-DOTATOC injection into the common hepatic artery. After receiving 13.3 GBq 213Bi-DOTATOC intraarterially into the shared feeder, complete responses were observed in the liver and the primary, which had been maintained for 28 months at the time of this report (Fig. 5).Fig. 4

Bottom Line: Chronic kidney toxicity was moderate.Acute haematotoxicity was even less pronounced than with the preceding beta therapies.TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120, Heidelberg, Germany, clemens.kratochwil@t-online.de.

ABSTRACT

Purpose: Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as (90)Y/(177)Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with (213)Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters.

Methods: Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with (90)Y/(177)Lu-DOTATOC were treated with an intraarterial infusion of (213)Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of (213)Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and (68)Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients.

Results: The biodistribution of (213)Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies.

Conclusion: TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses.

Show MeSH
Related in: MedlinePlus