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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 7 with an extensive tumour burden in the left liver lobe and multiple lesions in the right lobe, as well as disseminated bone marrow metastases predominantly in the spine and pelvis. These are demonstrated in coronal and sagittal 68Ga-DOTATOC-PET maximum intensity projections (a). As expected, liver metastases showed significant shrinkage after administration of 10.5 GBq of 213Bi-DOTATOC into the common hepatic artery. Additional systemic efficiency resulting from the 213Bi-DOTATOC reaching the systemic circulation after the first pass of the liver was noted after 6 months in that most of the bone marrow metastases had also diminished (b)
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Fig6: Patient 7 with an extensive tumour burden in the left liver lobe and multiple lesions in the right lobe, as well as disseminated bone marrow metastases predominantly in the spine and pelvis. These are demonstrated in coronal and sagittal 68Ga-DOTATOC-PET maximum intensity projections (a). As expected, liver metastases showed significant shrinkage after administration of 10.5 GBq of 213Bi-DOTATOC into the common hepatic artery. Additional systemic efficiency resulting from the 213Bi-DOTATOC reaching the systemic circulation after the first pass of the liver was noted after 6 months in that most of the bone marrow metastases had also diminished (b)

Mentions: Patient 6 presented with multiple progressive bulky liver metastases. Under therapy with 90Y-DOTATOC some parts of the tumour became necrotic but the major mass remained active (Fig. 2c). In escalating doses he received a cumulative dose of 20.6 GBq 213Bi-DOTATOC regionally into the liver artery. The previously hyperarterialized lesions changed to a devascularized mass, which showed stable disease after a follow-up of 31 months at the time of this report. Patient 7 presented with liver and bone metastases, but progressive liver metastases were considered to determine the prognosis. This patient had a history of grade IV haematotoxicity (thrombocytes <25,000/μl) after treatment with 90Y-DOTATOC. After receiving 13.7 GBq 213Bi-DOTATOC into the hepatic artery, substantial partial responses were observed in the liver and also the bone (Fig. 6) with striking disappearance of bone marrow lesions but with only grade II haematotoxicity. The patient had maintained the liver response for 24 months at the time of this report; extrahepatic progression occurred after 15 months.Fig. 6


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 7 with an extensive tumour burden in the left liver lobe and multiple lesions in the right lobe, as well as disseminated bone marrow metastases predominantly in the spine and pelvis. These are demonstrated in coronal and sagittal 68Ga-DOTATOC-PET maximum intensity projections (a). As expected, liver metastases showed significant shrinkage after administration of 10.5 GBq of 213Bi-DOTATOC into the common hepatic artery. Additional systemic efficiency resulting from the 213Bi-DOTATOC reaching the systemic circulation after the first pass of the liver was noted after 6 months in that most of the bone marrow metastases had also diminished (b)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4525192&req=5

Fig6: Patient 7 with an extensive tumour burden in the left liver lobe and multiple lesions in the right lobe, as well as disseminated bone marrow metastases predominantly in the spine and pelvis. These are demonstrated in coronal and sagittal 68Ga-DOTATOC-PET maximum intensity projections (a). As expected, liver metastases showed significant shrinkage after administration of 10.5 GBq of 213Bi-DOTATOC into the common hepatic artery. Additional systemic efficiency resulting from the 213Bi-DOTATOC reaching the systemic circulation after the first pass of the liver was noted after 6 months in that most of the bone marrow metastases had also diminished (b)
Mentions: Patient 6 presented with multiple progressive bulky liver metastases. Under therapy with 90Y-DOTATOC some parts of the tumour became necrotic but the major mass remained active (Fig. 2c). In escalating doses he received a cumulative dose of 20.6 GBq 213Bi-DOTATOC regionally into the liver artery. The previously hyperarterialized lesions changed to a devascularized mass, which showed stable disease after a follow-up of 31 months at the time of this report. Patient 7 presented with liver and bone metastases, but progressive liver metastases were considered to determine the prognosis. This patient had a history of grade IV haematotoxicity (thrombocytes <25,000/μl) after treatment with 90Y-DOTATOC. After receiving 13.7 GBq 213Bi-DOTATOC into the hepatic artery, substantial partial responses were observed in the liver and also the bone (Fig. 6) with striking disappearance of bone marrow lesions but with only grade II haematotoxicity. The patient had maintained the liver response for 24 months at the time of this report; extrahepatic progression occurred after 15 months.Fig. 6

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