Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies

Plaizier, M.A.B.D.; Jc, Roos; Teule, Gjj; Vandieren, Eb; Denhollander, W; Haisma, Hidde J.; Rl, DeJager; van-Lingen, Arthur

doi:10.1007/bf00188669

Cited by 10 publications

(4 citation statements)

References 17 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This statement must be qualified, however, in view of the limitations of the dosimetric techniques available for estimating the red marrow dose and the uncertainty concerning the biological efficacy of low-dose rate radiation. [51][52][53][54] The mean therapeutic ratio of radiation delivered to the marrow as compared to the liver of 3:1 was very similar to that reported by the Seattle team, whereas the therapeutic ratios for the lung (15:1) and for the kidney (2.1:1) were substiantially different, favoring the anti-CD66 antibody in the case of the lungs and the anti-CD45 antibody in the case of the kidneys. 22,24 For the anti-CD45 antibody, the liver was the dose-limiting organ in all but one of the patients.…”

Section: Discussionsupporting

confidence: 68%

Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study

Bunjes

Buchmann

Duncker

et al. 2001

Blood

162

100

View full text Add to dashboard Cite

The conditioning regimen prior to stem cell transplantation in 36 patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was intensified by treating patients with a rhenium 188-labeled anti-CD66 monoclonal antibody. Dosimetry was performed prior to therapy, and a favorable dosimetry was observed in all cases. Radioimmunotherapy with the labeled antibody provided a mean of 15.3 Gy of additional radiation to the marrow; the kidney was the normal organ receiving the highest dose of supplemental radiation (mean 7.4 Gy). Radioimmunotherapy was followed by standard full-dose conditioning with total body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide with or without thiotepa. Patients subsequently received a T-cell-depleted allogeneic graft from a HLA-identical family donor (n ‫؍‬ 15) or an alternative donor (n ‫؍‬ 17). In 4 patients without an allogeneic donor, an unmanipulated autologous graft was used. Infusion-related toxicity due to the labeled antibody was minimal, and no increase in treatment-related mortality due to the radioimmunoconjugate was observed. Day ؉30 and day ؉100 mortalities were 3% and 6%, respectively, and after a median follow-up of 18 months treatment-related mortality was 22%. Late renal toxicity was observed in 17% of patients. The relapse rate of 15 patients undergoing transplantation in first CR (complete remission) or second CR was 20%; 21 patients not in remission at the time of transplantation had a 30% relapse rate. (Blood. 2001;98:565-572)

show abstract

Section: Discussionsupporting

confidence: 68%

Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study

Bunjes

Buchmann

Duncker

et al. 2001

Blood

162

100

View full text Add to dashboard Cite

show abstract

“…A total residence time for the entire body of 113 h is obtained in the case of no biologic clearance. The red marrow dose was estimated using sampled blood clearance data (24,25). The red marrow concentration was assumed to be 30% of the blood activity concentration (conversion factor, 0.3).…”

Section: Internal Radiation Dosimetrymentioning

confidence: 99%

Radiation Dosimetry of ⁸⁹Zr-Labeled Chimeric Monoclonal Antibody U36 as Used for Immuno-PET in Head and Neck Cancer Patients

Börjesson¹,

Jauw²,

Bree³

et al. 2009

J Nucl Med

Self Cite

155

139

View full text Add to dashboard Cite

Immuno-PET is an appealing concept in the detection of tumors and planning of antibody-based therapy. For this purpose, the long-lived positron emitter 89 Zr (half-life, 78.4 h) recently became available. The aim of the present first-in-humans 89 Zr immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of the 89 Zr-labeled chimeric monoclonal antibody (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the performance of immuno-PET for detecting lymph node metastases was evaluated, as described previously. Methods: Twenty HNSCC patients, scheduled to undergo surgical tumor resection, received 75 MBq of 89 Zr-cmAb U36 (10 mg). Immuno-PET scans were acquired at 1, 24, 72, or 144 h after injection. The biodistribution of the radioimmunoconjugate was evaluated by ex vivo radioactivity measurement in blood and in biopsies from the surgical specimen obtained at 168 h after injection. Uptake levels and residence times in blood, tumors, and organs of interest were derived from quantitative immuno-PET studies, and absorbed doses were calculated using OLINDA/EXM 1.0. The red marrow dose was calculated using the residence time for blood. Results: 89 Zr-cmAb U36 was well tolerated by all subjects. PET quantification of blood-pool activity in the left ventricle of the heart showed a good agreement with sampled blood activity (difference equals 0.2% 6 16.9% [mean 6 SD]) except for heavyweight patients (.100 kg). A good agreement was also found for the assessment of mAb uptake in primary tumors (mean deviation, 28.4% 6 34.5%). The mean absorbed red marrow dose was 0.07 6 0.02 mSv/MBq and 0.09 6 0.01 mSv/MBq in men and women, respectively. The normal organ with the highest absorbed dose was the liver (mean dose, 1.25 6 0.27 mSv/MBq in men and 1.35 6 0.21 mSv/MBq in women), thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective dose was 0.53 6 0.03 mSv/MBq in men and 0.66 6 0.03 mSv/MBq in women. Measured excretion via the urinary tract was less than 3% during the first 72 h. Conclusion: 89 Zr immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose, justifying its further clinical exploitation in the detection of tumors and planning of mAbbased therapy. Monocl onal antibodies (mAbs) have been approved for use as diagnostics and therapeutics in a broad range of medical indications, but especially in oncology (1). Immuno-PET, the tracking and quantification of mAbs with PET in vivo, is an exciting novel option to improve diagnostic imaging and to guide mAb-based therapy and has been described previously (2-6).To enable PET of mAbs, an appropriate positron emitterwith a half-life (t 1/2 ) that is compatible with the time needed to achieve optimal tumor-to-nontumor ratios (typically 2-4 d for intact mAbs)-has to be securely coupled to the targeting molecule. 124 I (t 1/2 , 100.3 h) and 89 Zr (t 1/2 , 78.4 h) are particularly suitable in combination with intact mAbs, becaus...

show abstract

“…Estimation of marrow dose is a very difficult problem when the marrow is also the source organ [10]. However, since Quadramet targets bone rather than the marrow itself, reasonable dose estimates can be obtained [5].…”

Section: Dose Estimatesmentioning

confidence: 99%

Dosimetry and toxicity of Quadramet for bone marrow ablation in multiple myeloma and other haematological malignancies

Bartlett

Webb

Durrant

et al. 2002

European Journal of Nuclear Medicine and Molecular Imaging

View full text Add to dashboard Cite

Standard treatment regimens for haematological malignancies include myeloablative chemoradiotherapy and subsequent rescue by stem cell transplantation. However, these treatment regimens have significant associated mortality and morbidity, and disease recurrence remains a problem. One alternative approach is the targeted delivery of radiotherapy to the marrow using a bone-seeking agent labelled with an appropriate radioisotope, with the aim of delivering a potentially ablative radiation dose to marrow while minimising non-haematological toxicity. Pharmacokinetics and radiation dosimetry for a commercial preparation of samarium-153 ethylene diamine tetramethylene phosphonate (EDTMP; Quadramet) were evaluated in 43 tracer (average dose 740 MBq) studies of 42 patients with haematological malignancies. Measurements of 24-h retention were also available following infusion of 18-48 GBq in 15 patients. Quadramet cleared rapidly from the tissue, with a median biological half-life of 1.4 h. Activity taken up by the skeleton was firmly bound, with activity decreasing according to physical half-life at 24 h in 29 of the 43 cases. The percentage activity retained in the skeleton at 24 h with tracer doses was high (62%+/-13%), although this decreased to approximately 30% with therapy infusions. Because of this decrease in retention, the maximum feasible therapy activity for this formulation of Quadramet is 35 GBq. Median absorbed marrow radiation dose was 0.78 Gy/GBq in tracer studies: the decreased retention at high activities means that this corresponds to a median dose of 12 Gy for 35 GBq administered activity. It is possible to use 24-h retention as a rough guide to marrow dose in individual patients. In tracer studies, median bladder radiation dose was 0.22 Gy/GBq and radiation dose to the liver was very conservatively estimated at 0.2 Gy/GBq. After therapy infusions of up to 50 GBq in 37 patients, non-haematopoietic toxicity was not seen in any patient. In addition, myelosuppression was achieved without evidence of myelofibrosis. The residual dose rate to marrow fell to a level acceptable for stem cell re-infusion by 2 weeks after administration.

show abstract

Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies

Cited by 10 publications

References 17 publications

Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study

Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study

Radiation Dosimetry of ⁸⁹Zr-Labeled Chimeric Monoclonal Antibody U36 as Used for Immuno-PET in Head and Neck Cancer Patients

Dosimetry and toxicity of Quadramet for bone marrow ablation in multiple myeloma and other haematological malignancies

Contact Info

Product

Resources

About

Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies

Cited by 10 publications

References 17 publications

Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study

Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study

Radiation Dosimetry of 89Zr-Labeled Chimeric Monoclonal Antibody U36 as Used for Immuno-PET in Head and Neck Cancer Patients

Dosimetry and toxicity of Quadramet for bone marrow ablation in multiple myeloma and other haematological malignancies

Contact Info

Product

Resources

About

Radiation Dosimetry of ⁸⁹Zr-Labeled Chimeric Monoclonal Antibody U36 as Used for Immuno-PET in Head and Neck Cancer Patients