Radiation dose estimation using preclinical imaging with ‐metaiodobenzylguanidine (MIBG) PET

Lee, Chang-Lae; Wahnishe, Hilla; Sayre, George A.; Cho, Hyo-Min; Kim, Hee-Joung; Hernandez-Pampaloni, Miguel; Hawkins, Randall A.; Dannoon, Shorouk; VanBrocklin, Henry F.; Itsara, Melissa; Weiss, William A.; Yang, Xiaodong; Haas‐Kogan, Daphne A.; Matthay, Katherine K.; Seo, Youngho

doi:10.1118/1.3480965

Cited by 61 publications

(38 citation statements)

References 31 publications

(20 reference statements)

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“…In this study we have used 5 animals per tracer, analyzed at three time-points. This are in agreement with other studies were the number of animals per time point typically are between 3-6, with the number of time points between 3 and 7 [20,21,26,27]. Despite the relatively low number of data points in this study (1, 4.5 and 22 h) it seems that three data points are sufficient considering the relatively high concordance between predicted and observed total body dosimetry values for 64 Cu-DOTA-TATE (Fig.…”

Section: Discussionsupporting

confidence: 93%

“…Despite the obvious differences in anatomy and physiology between mice and man, relatively close correlation between predicted vs. observed dosimetry have however been found, exemplified by close predictions of 4 out of 6 PET tracers in the study by Sakata and co-workers [22]. Moreover, recently two studies have reported the use of PET image-derived biodistribution analysis in mice for use to estimate human dosimetry [26,27]. Importantly, a significant correlation between conventional biodistribution tissue analysis and image-derived analysis were reported (p = 0.9666), thus validating this new approach [27].…”

Section: Introductionmentioning

confidence: 89%

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Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

Persson

Ali

Binderup

et al. 2014

Nuclear Medicine and Biology

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 89%

Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

Persson

Ali

Binderup

et al. 2014

Nuclear Medicine and Biology

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“…This is likely due to differences in tumor perfusion, proportion of viable tumor cells, biologic body clearance rate, and tumor avidity and retention of MIBG. Perhaps improving the accuracy of the dosimetry with SPECT (22) or using 124 I-MIBG with PET would increase correlation between activity and response (23). Overall, the measurable tumors all received significant doses, with a median tumor dose of 49 Gy, more than twice the standard dose applied currently by external-beam radiation for newly diagnosed patients with high-risk disease (24).…”

Section: Discussionmentioning

confidence: 99%

Dose Escalation Study of No-Carrier-Added ¹³¹I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

Matthay¹,

Weiss²,

Villablanca³

et al. 2012

J Nucl Med

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and 14 Molecular Insight Pharmaceuticals, Cambridge, Massachusetts 131 I-metaiodobenzylguanidine (MIBG) is specifically taken up in neuroblastoma, with a response rate of 20%-37% in relapsed disease. Nonradioactive carrier MIBG molecules inhibit uptake of 131 I-MIBG, theoretically resulting in less tumor radiation and increased risk of cardiovascular toxicity. Our aim was to establish the maximum tolerated dose of nocarrier-added (NCA) 131 I-MIBG, with secondary aims of assessing tumor and organ dosimetry and overall response. Methods: Eligible patients were 1-30 y old with resistant neuroblastoma, 131 I-MIBG uptake, and cryopreserved hematopoietic stem cells. A diagnostic dose of NCA 131 I-MIBG was followed by 3 dosimetry scans to assess radiation dose to critical organs and soft-tissue tumors. The treatment dose of NCA 131 I-MIBG (specific activity, 165 MBq/mg) was adjusted as necessary on the basis of critical organ tolerance limits. Autologous hematopoietic stem cells were infused 14 d after therapy to abrogate prolonged myelosuppression. Response and toxicity were evaluated on day 60. The NCA 131 I-MIBG was escalated from 444 to 777 MBq/kg (12-21 mCi/kg) using a 3 1 3 design. Dose-limiting toxicity (DLT) was failure to reconstitute neutrophils to greater than 500/mL within 28 d or platelets to greater than 20,000/mL within 56 d, or grade 3 or 4 nonhematologic toxicity by Common Terminology Criteria for Adverse Events (version 3.0) except for predefined exclusions. Results: Three patients each were evaluable at 444, 555, and 666 MBq/kg without DLT. The dose of 777 MBq/kg dose was not feasible because of organ dosimetry limits; however, 3 assigned patients were evaluable for a received dose of 666 MBq/kg, providing a total of 6 patients evaluable for toxicity at 666 MBq/kg without DLT. Mean whole-body radiation was 0.23 mGy/MBq, and mean organ doses were 0.92, 0.82, and 1.2 mGy/MBq of MIBG for the liver, lung, and kidney, respectively. Eight patients had 13 soft-tissue lesions with tumor-absorbed doses of 26-378 Gy. Four of 15 patients had a complete (n 5 1) or partial (n 5 3) response, 1 had a mixed response, 4 had stable disease, and 6 had progressive disease. Conclusion: NCA 131 I-MIBG with autologous peripheral blood stem cell transplantation is feasible at 666 MBq/kg without significant nonhematologic toxicity and with promising activity.

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“…Pretherapeutic imaging to estimate disease distribution and burden is possible with high sensitivity in both neuroblastoma and PHEO patients (48,49). Radiation dosimetry predicted from animal data was favorable, with mean effective doses ranging from 0.34 mSv/MBq for adults to 1.9-3.75 for children 1 y old or younger (135). In a preclinical xenograft model for neuroblastoma, the radiation dose in tumors and organs was determined.…”

Section: Strategies For Improving Net Targeting and Dose Delivery Witmentioning

confidence: 99%

Norepinephrine Transporter as a Target for Imaging and Therapy

Pandit‐Taskar

Modak

2017

J Nucl Med

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The norepinephrine transporter (NET) is essential for norepinephrine uptake at the synaptic terminals and adrenal chromaffin cells. In neuroendocrine tumors, NET can be targeted for imaging as well as therapy. One of the most widely used theranostic agents targeting NET is metaiodobenzylguanidine (MIBG), a guanethidine analog of norepinephrine. 123 I/ 131 I-MIBG theranostics have been applied in the clinical evaluation and management of neuroendocrine tumors, especially in neuroblastoma, paraganglioma, and pheochromocytoma. 123 I-MIBG imaging is a mainstay in the evaluation of neuroblastoma, and 131 I-MIBG has been used for the treatment of relapsed high-risk neuroblastoma for several years, however, the outcome remains suboptimal. 131 I-MIBG has essentially been only palliative in paraganglioma/pheochromocytoma patients. Various techniques of improving therapeutic outcomes, such as dosimetric estimations, high-dose therapies, multiple fractionated administration and combination therapy with radiation sensitizers, chemotherapy, and other radionuclide therapies, are being evaluated. PET tracers targeting NET appear promising and may be more convenient options for the imaging and assessment after treatment. Here, we present an overview of NET as a target for theranostics; review its current role in some neuroendocrine tumors, such as neuroblastoma, paraganglioma/ pheochromocytoma, and carcinoids; and discuss approaches to improving targeting and theranostic outcomes.

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Radiation dose estimation using preclinical imaging with ‐metaiodobenzylguanidine (MIBG) PET

Abstract: The authors estimated human-equivalent internal radiation dose of 124I-MIBG using preclinical imaging data. As a reference, the effective dose estimation showed that 124I-MIBG would deliver less radiation dose than 124I-NaI, a radiotracer already being used in patients with thyroid cancer.

Cited by 61 publications

References 31 publications

Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

Dose Escalation Study of No-Carrier-Added ¹³¹I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

Norepinephrine Transporter as a Target for Imaging and Therapy

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Radiation dose estimation using preclinical imaging with ‐metaiodobenzylguanidine (MIBG) PET

Cited by 61 publications

References 31 publications

Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

Dose Escalation Study of No-Carrier-Added 131I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

Norepinephrine Transporter as a Target for Imaging and Therapy

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Dose Escalation Study of No-Carrier-Added ¹³¹I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial