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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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Diagnostic 68Ga-DOTATOC PET scans in NET patients 1, 2 and 6 (a, b, c). d In patient 1 the largest lesion was highly selectively cannulated for intraarterial administration of 213Bi-DOTATOC (top left); 440 keV SPECT scan (bottom left) and whole-body planar (right) scans 45 min after injection demonstrate peak uptake in the target lesion in liver segment 6. e Patient 2 received two therapeutic injections, one into liver segments 5 – 8 (top left) and one into segment 4a/b (top right); 440 keV emission scans (bottom left and right) 045 min after injection show the impact of intraarterial administration for fast tumour targeting and regionally intensified peptide accumulation. f In whole-liver treatment (patient 6) the hepatic biodistribution of 213Bi-DOTATOC is the same as the distribution of 68Ga-DOTATOC, but in comparison to systemic treatment spares the spleen
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Fig2: Diagnostic 68Ga-DOTATOC PET scans in NET patients 1, 2 and 6 (a, b, c). d In patient 1 the largest lesion was highly selectively cannulated for intraarterial administration of 213Bi-DOTATOC (top left); 440 keV SPECT scan (bottom left) and whole-body planar (right) scans 45 min after injection demonstrate peak uptake in the target lesion in liver segment 6. e Patient 2 received two therapeutic injections, one into liver segments 5 – 8 (top left) and one into segment 4a/b (top right); 440 keV emission scans (bottom left and right) 045 min after injection show the impact of intraarterial administration for fast tumour targeting and regionally intensified peptide accumulation. f In whole-liver treatment (patient 6) the hepatic biodistribution of 213Bi-DOTATOC is the same as the distribution of 68Ga-DOTATOC, but in comparison to systemic treatment spares the spleen

Mentions: Time–activity curves in blood, as presented in Supplementary Fig. 3, were similar to data reported in the literature for intravenously administered diagnostic somatostatin analogues [23, 24]. Within the first half-life of the radionuclide an average of 15.1 ± 7.7 % (range 0.1 – 35.4 %) was eliminated in the urine. The 440 keV gamma coemission of 213Bi was sufficient to acquire evaluable planar and SPECT scans in patients undergoing therapy at all injected activities. Coreading with the pretherapeutic 68Ga-DOTATOC PET scans validated specific binding at the tumour sites (Fig. 2).Fig. 2


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)

Diagnostic 68Ga-DOTATOC PET scans in NET patients 1, 2 and 6 (a, b, c). d In patient 1 the largest lesion was highly selectively cannulated for intraarterial administration of 213Bi-DOTATOC (top left); 440 keV SPECT scan (bottom left) and whole-body planar (right) scans 45 min after injection demonstrate peak uptake in the target lesion in liver segment 6. e Patient 2 received two therapeutic injections, one into liver segments 5 – 8 (top left) and one into segment 4a/b (top right); 440 keV emission scans (bottom left and right) 045 min after injection show the impact of intraarterial administration for fast tumour targeting and regionally intensified peptide accumulation. f In whole-liver treatment (patient 6) the hepatic biodistribution of 213Bi-DOTATOC is the same as the distribution of 68Ga-DOTATOC, but in comparison to systemic treatment spares the spleen
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Related In: Results  -  Collection

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Fig2: Diagnostic 68Ga-DOTATOC PET scans in NET patients 1, 2 and 6 (a, b, c). d In patient 1 the largest lesion was highly selectively cannulated for intraarterial administration of 213Bi-DOTATOC (top left); 440 keV SPECT scan (bottom left) and whole-body planar (right) scans 45 min after injection demonstrate peak uptake in the target lesion in liver segment 6. e Patient 2 received two therapeutic injections, one into liver segments 5 – 8 (top left) and one into segment 4a/b (top right); 440 keV emission scans (bottom left and right) 045 min after injection show the impact of intraarterial administration for fast tumour targeting and regionally intensified peptide accumulation. f In whole-liver treatment (patient 6) the hepatic biodistribution of 213Bi-DOTATOC is the same as the distribution of 68Ga-DOTATOC, but in comparison to systemic treatment spares the spleen
Mentions: Time–activity curves in blood, as presented in Supplementary Fig. 3, were similar to data reported in the literature for intravenously administered diagnostic somatostatin analogues [23, 24]. Within the first half-life of the radionuclide an average of 15.1 ± 7.7 % (range 0.1 – 35.4 %) was eliminated in the urine. The 440 keV gamma coemission of 213Bi was sufficient to acquire evaluable planar and SPECT scans in patients undergoing therapy at all injected activities. Coreading with the pretherapeutic 68Ga-DOTATOC PET scans validated specific binding at the tumour sites (Fig. 2).Fig. 2

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