¹⁷⁷Lu-EDTMP: A Viable Bone Pain Palliative in Skeletal Metastasis

Abstract

Anti-CD20 monoclonal antibodies (mAbs), unlabeled rituximab (Rituxan, Biogen Idec Inc., Cambridge, MA; and Genentech Inc., South San Francisco, CA) or radiolabeled 90Y-ibritumomab (Zevalin, Biogen Idec Inc., Cambridge, MA) and 131I-tositumomab (Bexxar; Glaxo Smith Kline, Research Triangle Park, NC), have proven to be effective therapy for non-Hodgkin's lymphoma (NHL), but also induce immediate and persistent decreases in normal peripheral blood lymphocytes (PBLs). Lym-1, a mAb that selectively targets malignant lymphocytes, also has induced therapeutic responses and prolonged survival in patients with NHL when labeled with iodine-131 (131I). We have retrospectively examined its effect on PBLs in 41 NHL patients that had received 131I-Lym-1 therapy. Absolute lymphocyte counts (ALCs) were evaluated before and after the first and last 131I-Lym-1 infusion. Modest decreases in PBLs were observed in most of the patients. Using strict criteria to define recovery, time to recovery was determined for 19 patients, with the remainder censored because of insufficient follow-up (median follow up for censored patients: 22 days). Using Kaplan-Meier estimates, it would be predicted that 31% of patients would recover by 28 days and that median time to recovery would be 44 days after the last 131I-Lym-1 infusion. No predictors were found for time to recovery, considering such factors as the administered Lym-1 or 131I dose, spleen volume, or radiation doses to the body, marrow, or spleen. The data suggest that the effect of 131I-Lym-1 on ALC is the result of a nonspecific radiation effect, rather than a specific Lym-1 mAb effect. The shorter time required for ALC recovery after 131I-Lym-1 when compared to that reported for anti-CD20 mAbs, whether radiolabeled or otherwise, is probably related to differing mechanisms for lymphocytotoxicity and lesser Lym-1 antigenic density on normal B-lymphocytes.

Clinical Efficacy and Safety Comparison of 177Lu-EDTMP with 153Sm-EDTMP on an Equidose Basis in Patients with Painful Skeletal Metastases

“…There was no significant background activity 3 h after injection, suggesting rapid clearance of complex from the circulation. Skeletal activity was retained until 7 d after injection (14,23). Our present study compared the clinical efficacy and safety of 177 Lu-EDTMP with that of 153 Sm-EDTMP in patients with painful skeletal metastasis from various malignancies.…”

“…153 Sm-EDTMP (mean b-energy, 233 keV; half-life, 1.9 d; g-energy, 103 keV), with its short b-range emission, has advantages over radionuclides with high b-energy in terms of reduced incidence of bone marrow suppression. 177 Lu chelated with EDTMP is a new and relatively inexpensive bone-seeking radiopharmaceutical and can be potentially useful for systemic therapy in patients with bone metastases (13)(14)(15). 177 Lu-EDTMP (maximum b-energy, 497 keV; half-life, 6.7 d, g-energy, 208 keV), with its short b-range emission and half-life of 6.7 d, may be a useful alternative to 153 Sm-EDTMP for systemic radionuclide therapy with logistical advantages due to the relatively longer half-life of 177 Lu; furthermore, 177 Lu labeling with other ligands such as DOTATATE (for neuroendocrine tumors) and prostate-specific membrane antigen (for prostatic carcinoma) make it more attractive for an active therapeutic nuclear medicine program.…”

Production of 177Lu for Targeted Radionuclide Therapy: Available Options

“…The in vivo applications of key 177 Lu radiopharmaceuticals for a variety of therapeutic procedures include peptide receptor radionuclide therapy [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26], bone pain palliation [27][28][29][30][31][32][33], radiation synovectomy [34][35][36][37][38][39] and radioimmonutherapy [40][41][42][43][44][45][46]. There is a steadily expanding list of 177 Lu-labeled radiopharmaceuticals that is currently being evaluated at the preclinical research or at product development stages; these may potentially be used in vivo in humans for evaluation for radionuclide therapy [1][2][3].…”

177Lu-EDTMP for palliation of pain from bone metastases in patients with prostate and breast cancer: a phase II study

“…Some studies have shown that bone-targeted therapy also has the potential to delay progression of osseous metastases [7][8][9]. Preclinical studies have outlined the prospects for 177 Lu-EDTMP for systemic radionuclide therapy in patients with breast or hormone-refractory prostate cancer and bone metastases [10]. The tissue penetration range of the β particles from 177 Lu are low ensuring less bone marrow suppression, a major advantage of this radiotherapeutic [11].…”