RT Journal Article
SR Electronic
T1 Radioimmunotherapy of Non-Hodgkin’s Lymphoma with <sup>90</sup>Y-DOTA Humanized Anti-CD22 IgG (<sup>90</sup>Y-Epratuzumab): Do Tumor Targeting and Dosimetry Predict Therapeutic Response?
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 2000
OP 2018
VO 44
IS 12
A1 Sharkey, Robert M.
A1 Brenner, Arnold
A1 Burton, Jack
A1 Hajjar, George
A1 Toder, Stephen P.
A1 Alavi, Abass
A1 Matthies, Alexander
A1 Tsai, Donald E.
A1 Schuster, Stephen J.
A1 Stadtmauer, Edward A.
A1 Czuczman, Myron S.
A1 Lamonica, Dominick
A1 Kraeber-Bodere, Françoise
A1 Mahe, Beatrice
A1 Chatal, Jean-François
A1 Rogatko, André
A1 Mardirrosian, George
A1 Goldenberg, David M.
YR 2003
UL http://jnm.snmjournals.org/content/44/12/2000.abstract
AB A DOTA (1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid)-conjugated, 111In- and 90Y-labeled humanized antibody to CD22, epratuzumab, was studied in patients with non-Hodgkin’s lymphoma (NHL) to assess biodistribution and tumor targeting, pharmacokinetics, dosimetry, and anti-antibody response. Of particular interest was to evaluate whether pretherapy targeting and tumor dosimetry could predict therapeutic responses. Methods: Patients received a pretherapy imaging study with 111In-DOTA-epratuzumab IgG (0.75 mg/kg), followed about 1 wk later with 90Y-DOTA-epratuzumab starting at a dose level of 0.185 GBq/m2 (5 mCi/m2) in patients who had prior high-dose chemotherapy (group 2), and at 0.370 GBq/m2 in patients who did not have a prior transplant (group 1), with escalation in 0.185-GBq/m2 increments. Results: The effective blood half-life for 111In-DOTA epratuzumab was 36.1 ± 7.9 h (n = 25) compared with 35.2 ± 7.0 h for 90Y-DOTA-epratuzumab (n = 22). The whole-body half-life for 90Y-DOTA-epratuzumab estimated from 111In-DOTA-epratuzumab scintigraphy was 58.3 ± 4.7 h (n = 20), with urine collection confirming the loss of between 2.2% and 15.9% of the injected activity over 3 d (n = 3). One-hundred sixteen of 165 CT-confirmed lesions were visualized with 111In-DOTA-epratuzumab. Radiation-absorbed doses to liver, lungs, and kidneys averaged 0.55 ± 0.13 (n = 17), 0.28 ± 0.06 (n = 17), and 0.38 ± 0.07 mGy/MBq (n = 10), respectively, with 0.14 ± 0.02 and 0.23 ± 0.04 mGy/MBq delivered to the whole-body and red marrow, respectively. Tumor doses (n = 14 lesions in 10 patients) ranged from 1.0 to as much as 83 mGy/MBq for a 0.5-g lesion (median, 7.15 mGy/MBq). Group 2 patients were more likely to experience significant hematologic toxicities, but doses of up to 0.370 GBq/m2 of 90Y-DOTA-epratuzumab were tolerated with standard support measures, whereas patients in group 1 tolerated doses of up to 0.740 GBq/m2 with the potential for further escalation. Anti-tumor effects were seen in both indolent and aggressive NHL. The data also suggest that anti-tumor responses of potentially equal magnitude can occur irrespective of tumor targeting and tumor size. Hence, tumor response did not correlate with the radiation dose delivered or with the tumor being visualized by external imaging. An anti-antibody response to epratuzumab was detected by an enzyme-linked immunosorbent assay in only 2 of 16 patients. Conclusion: These results suggest that 90Y-DOTA-epratuzmab is a promising agent for the treatment of NHL and warrants further study. There was evidence suggesting that in this system, factors other than tumor radiation dose and targeting may be involved in the success of radioimmunotherapy.