Dataset Information

Biodistribution and Dosimetry of Intraventricularly Administered ¹²⁴I-Omburtamab in Patients with Metastatic Leptomeningeal Tumors.

ABSTRACT: Radiation dose estimations are key for optimizing therapies. We studied the role of ¹²⁴I-omburtamab (8H9) given intraventricularly in assessing the distribution and radiation doses before ¹³¹I-omburtamab therapy in patients with metastatic leptomeningeal disease and compared it with the estimates from cerebrospinal fluid (CSF) sampling. Methods: Patients with histologically proven malignancy and metastatic disease to the central nervous system or leptomeninges who met eligibility criteria for ¹³¹I-omburtamab therapy underwent immuno-PET imaging with ¹²⁴I-8H9 followed by ¹³¹I-8H9 antibody therapy. Patients were imaged with approximately 74 MBq of intraventricular ¹²⁴I-omburtamab via an Ommaya reservoir. Whole-body PET images were acquired at approximately 4, 24, and 48 h after administration and analyzed for dosimetry calculations. Peripheral blood and CSF samples were obtained at multiple time points for dosimetry estimation. Results: Forty-two patients with complete dosimetry and therapy data were analyzed. ¹²⁴I-omburtamab PET-based radiation dosimetry estimations revealed mean (±SD) absorbed dose to the CSF for ¹³¹I-8H9 of 0.62 ± 0.40 cGy/MBq, compared with 2.22 ± 2.19 cGy/MBq based on ¹²⁴I-omburtamab CSF samples and 1.53 ± 1.37 cGy/MBq based on ¹³¹I-omburtamab CSF samples. The mean absorbed dose to the blood was 0.051 ± 0.11 cGy/MBq for ¹²⁴I-omburtamab samples and 0.07 ± 0.04 cGy/MBq for ¹³¹I-omburtamab samples. The effective whole-body radiation dose for ¹²⁴I-omburtamab was 0.49 ± 0.27 mSv/MBq. The mean whole-body clearance half-time was 44.98 ± 16.29 h. Conclusion: PET imaging with ¹²⁴I-omburtamab antibody administered intraventricularly allows for noninvasive estimation of dose to CSF and normal organs. High CSF-to-blood absorbed-dose ratios are noted, allowing for an improved therapeutic index to leptomeningeal disease and reduced systemic doses. PET imaging-based estimates were less variable and more reliable than CSF sample-based dosimetry.

SUBMITTER: Pandit-Taskar N

PROVIDER: S-EPMC6894373 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Biodistribution and Dosimetry of Intraventricularly Administered 124I-Omburtamab in Patients with Metastatic Leptomeningeal Tumors.

Pandit-Taskar Neeta N Zanzonico Pat B PB Kramer Kim K Grkovski Milan M Fung Edward K EK Shi Weiji W Zhang Zhigang Z Lyashchenko Serge K SK Fung Alex M AM Pentlow Keith S KS Carrasquillo Jorge A JA Lewis Jason S JS Larson Steven M SM Cheung Nai-Kong V NV Humm John L JL

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20190812 12

Radiation dose estimations are key for optimizing therapies. We studied the role of 124I-omburtamab (8H9) given intraventricularly in assessing the distribution and radiation doses before 131I-omburtamab therapy in patients with metastatic leptomeningeal disease and compared it with the estimates from cerebrospinal fluid (CSF) sampling. Methods: Patients with histologically proven malignancy and metastatic disease to the central nervous system or leptomeninges who me ...[more]

PMID: 31405921

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Project description:PurposeSomatostatin receptor antagonists have shown promise for imaging neuroendocrine tumors (NETs) in preclinical studies, but clinical data is still very limited. In this study, we assess the feasibility of using the novel somatostatin antagonist 68Ga-DOTA-JR11 for PET imaging of NETs.MethodsTwenty patients with advanced NETs underwent whole-body PET/CT imaging 60 min after injection of 169 MBq (median) 68Ga-DOTA-JR11 as part of a prospective study. Volumes of interest were drawn around up to four 68Ga-DOTA-JR11-avid lesions per patient (with uptake greater than liver) and standardized uptake values were estimated. Additionally, target-to-normal tissue ratios were calculated. A subset of six patients had additional imaging (25-min dynamic scan of the upper abdomen including, at least partly, cardiac left ventricle, liver, spleen, and kidney, and a whole-body PET/CT scan at 30 min post-injection) to determine the time course of tracer distribution and facilitate radiation dose estimates. Absorbed doses were calculated using OLINDA/EXM 1.0.ResultsIn contrast to the known biodistribution of somatostatin receptor agonists, little or no uptake above background was seen in the pituitary gland, spleen, adrenals, and uninvolved liver; e.g., median spleen SUVmean 1.4 (range: 0.7-1.8), liver SUVmean 1.1 (0.7-1.9). A total of 42 tumor lesions were analyzed with median SUVmax 13.0 (range: 2.9-94), TNR blood 9.3 (1.8-87), TNR spleen 4.9 (1.9-48), TNR kidney 2.2 (0.52-28), and TNR liver 10.5 (2.3-107). Tumor uptake reached plateau levels by 20-30 min post-injection. The highest absorbed dose estimates (mGy/MBq) to normal tissues were: urinary bladder wall (0.30; SD 0.06) and kidneys (0.050; SD 0.013). The effective dose (ICRP 103) was 0.022 (SD 0.003) mSv/MBq.Conclusions68Ga-DOTA-JR11 demonstrated rapid tumor uptake, high tumor/background ratios, and rapid clearance from blood. The low liver background is advantageous and may facilitate detection of liver metastases. Dosimetric data compare favorably with published data for 68Ga-DOTATATE and 68Ga-DOTATOC.

Project description:PurposeThere is a continuous search for imaging techniques with high sensitivity and specificity for brain tumors. Positron emission tomography (PET) imaging has shown promise, though many PET agents either have a low tumor specificity or impractical physical half-lives. [124I]CLR1404 is a small molecule alkylphosphocholine analogue that is thought to bind to plasma membrane lipid rafts and has shown high tumor-to-background ratios (TBR) in a previous pilot study in brain tumor patients. This study attempts to define the clinical value of [124I]CLR1404 PET/CT (aka CLR124).ProceduresAdult patients with new or suspected recurrence of high-grade primary or metastatic brain tumors (N = 27) were injected with [124I]CLR1404 followed by PET/CT at 6, 24, and 48 h. Standard uptake values (SUV) and TBR values were calculated for all time points. Uptake of [124I]CLR1404 was qualitatively assessed, compared with magnetic resonance imaging (MRI), and correlated with clinical outcome. Final diagnosis (N = 25) was established based on surgically resected tissue or long-term follow-up.ResultsPositive uptake with high TBR was detected in all but one patient with a final diagnosis of primary/recurrent brain tumor (12/13) and in less than half of patients with treatment-related changes (5/12). Concordance between [124I]CLR1404 uptake and contrast enhancement on MRI was seen in < 40 %, with no concordance between T2-hyperintensities and uptake. No significant difference in overall outcome was found between patients with and without [124I]CLR1404 uptake.ConclusionsThe uptake pattern in these patients suggests a very high sensitivity of [124I]CLR1404 PET/CT for diagnosing tumor tissue; however, tumor specificity needs to be further defined. Relative lack of concordance with standard MRI characteristics suggests that [124I]CLR1404 PET/CT provides additional information about brain tumors compared to MRI alone, potentially improving clinical decision-making.

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Dataset Information

Biodistribution and Dosimetry of Intraventricularly Administered ¹²⁴I-Omburtamab in Patients with Metastatic Leptomeningeal Tumors.

Publications

Biodistribution and Dosimetry of Intraventricularly Administered <sup>124</sup>I-Omburtamab in Patients with Metastatic Leptomeningeal Tumors.

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