Adverse Events in the Long-Term Follow-Up of Patients Treated With Samarium Sm 153 Lexidronam for Osseous Metastases

Paravati, Anthony J.; Russo, Andrea; Aitken, Candice L.

doi:10.1016/j.ijrobp.2010.05.066

Cited by 6 publications

(4 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hematologic recovery is generally complete by 8 weeks. More prolonged and pronounced myelosuppression can be seen in heavily pretreated patients or patients with other bone marrow comorbidities [ 16 ], but with appropriate monitoring patients have safely received 153 Sm-EDTMP before or after chemotherapy and EBRT [ 17 , 18 ]. A dose of 3 mCi/kg (111 MBq/kg) causes frequent grade III–IV thrombocytopenia and neutropenia [ 19 , 20 ].…”

Section: Properties Of 153 Sm-edtmpmentioning

confidence: 99%

Beyond Palliation: Therapeutic Applications Of 153Samarium-EDTMP

Wilky¹

2013

Clin Exp Pharmacol

View full text Add to dashboard Cite

Primary and metastatic malignant bone lesions result in significant pain and disability in oncology patients. Targeted bone-seeking radioisotopes including 153Samarium ethylene-diamine-tetramethylene-phosphonic acid (153Sm-EDTMP) have been shown to effectively palliate bone pain, often when external beam radiotherapy (EBRT) is not feasible. However, recent evidence also suggests 153Sm-EDTMP has cytotoxic activity either alone or in combination with chemotherapy or EBRT. 153Sm-EDTMP may be useful as anti-neoplastic therapy apart from pain palliation in a variety of malignancies. For prostate cancer patients, several phase I and II clinical trials have shown that combined 153Sm-EDTMP and docetaxel-based chemotherapy can result in >50% decrease in prostate-specific antigen with manageable myelosuppression. In hematologic malignancies, 153Sm-EDTMP produced clinical responses when combined with bortezomib in multiple myeloma. 153Sm-EDTMP also can be used with myeloablative chemotherapy for marrow conditioning prior to stem cell transplant. In osteosarcoma, 153Sm-EDTMP infusion delivers radiation to multiple unresectable lesions simultaneously and provides local cytotoxicity without soft tissue damage that can be combined with chemotherapy or radiation. Prior to routine incorporation of 153Sm-EDTMP into therapeutic regimens, we must learn how to ensure optimal delivery to tumors, determine which patients are likely to benefit, improve our ability to assess clinical response in bone lesions and further evaluate the efficacy 153Sm-EDTMP in combination with chemotherapy, radiation and novel targeted agents.

show abstract

Section: Properties Of 153 Sm-edtmpmentioning

confidence: 99%

Beyond Palliation: Therapeutic Applications Of 153Samarium-EDTMP

Wilky¹

2013

Clin Exp Pharmacol

View full text Add to dashboard Cite

show abstract

“…1,2 The selective uptake of targeted radioisotopes into areas of high bone turnover can effectively decrease pain and slow tumor progression, but proximity to the bone marrow can also cause myelosuppression thus limiting the ability to deliver concurrent systemic chemotherapy to combat the soft tissue component of the cancer. [1][2][3][4] Several radiopharmaceuticals have been used for skeletal-targeted radiotherapy. Samarium-153 is a lanthanide, or rare earth element (also called a radiometal) that emits beta particles with an average energy of 223.6 keV and a maximum energy of 808.2 keV, as well as a 103 keV gamma ray (30% abundance).…”

Section: Introductionmentioning

confidence: 99%

“…Radiopharmaceutical therapy targeted to the skeleton exploits dynamic changes in the tumor microenvironment in which there is constant lysis and proliferation, unlike the relatively slow and minimally active bone turnover in adjacent and distant normal bone 1,2 . The selective uptake of targeted radioisotopes into areas of high bone turnover can effectively decrease pain and slow tumor progression, but proximity to the bone marrow can also cause myelosuppression thus limiting the ability to deliver concurrent systemic chemotherapy to combat the soft tissue component of the cancer 1–4 …”

Section: Introductionmentioning

confidence: 99%

Phase I evaluation of CycloSam^® (Sm‐153‐DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma

Selting

Simón

Lattimer

et al. 2023

Vet Radiology Ultrasound

View full text Add to dashboard Cite

Abstract153Sm‐DOTMP (CycloSam®) is a newly‐patented radiopharmaceutical for bone tumor treatment. DOTMP (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetramethylene‐phosphonate) is a macrocyclic chelating agent with superior binding properties to 153Sm when compared with EDTMP (Quadramet™, used for palliative treatment of bone cancer). CycloSam® was administered at 1 mCi/kg (37 MBq/kg) in a prospective pilot study to seven dogs with bone cancer resulting in no myelosuppression. Then, 13 dogs were enrolled in a prospective clinical trial study using traditional 3+3 dose escalation and starting at 1.5 mCi/kg. Baseline evaluation included hematologic and biochemical testing, diagnosis confirmation, thoracic and limb radiographs, technetium‐99 m‐HDP bone scintigraphy, and 18F‐FDG PET scan (SUVmax). Toxicity (primary endpoint) was assessed through weekly blood counts and adverse events. Dogs received 1.5 mCi/kg (n = 4), 1.75 mCi/kg (n = 6), and 2 mCi/kg (n = 3) of 153Sm‐DOTMP. Dose‐limiting neutropenia and thrombocytopenia were seen at 2 mCi/kg. No dose‐limiting nonhematologic toxicities occurred. Efficacy (secondary endpoint) was assessed by objective lameness measurement (body‐mounted inertial sensors), owner quality‐of‐life (QoL) questionnaire, and repeat PET scan. Objective lameness measurement improved in four dogs (53%–60% decrease) was equivocal in three dogs, and worsened in four dogs (66%–115% increase); two dogs were not evaluable. Repeat 18F‐FDG PET scan results varied and change in lameness did not consistently correlate with SUVmax changes. QoL score worsened (n = 5) or was improved/stable (n = 7). Carboplatin chemotherapy (300 mg/m2 IV every 3 weeks ×4) started 4 weeks after 153Sm‐DOTMP injection. No dog died of chemotherapy‐related complications. All dogs completed study monitoring. The recommended dose for CycloSam® in dogs is 1.75 mCi/kg, which resulted in some pain control with minimal toxicity and was safely combined with chemotherapy.

show abstract

“…Various radiopharmaceuticals are in clinical use like [ 153 Sm]ethylene diamine tetramethylene phosphonate (Quadramet) and rhenium-186-hydroxyethylidenediphosphonic acid ([ 186 Re]-HEDP), all having unique characteristics (9, 10). …”

Section: Introductionmentioning

confidence: 99%

[68Ga]/[188Re] Complexed [CDTMP] Trans-1,2-Cyclohexyldinitrilotetraphosphonic Acid As a Theranostic Agent for Skeletal Metastases

et al. 2017

View full text Add to dashboard Cite

ObjectiveMetastasis of the osseous tissue is one of the frequent and severe aggravations as a result of several neoplastic conditions, such as metabolic disorders, infections, and cancer. The objective of this study was to evaluate the pertinence of [68Ga]-trans-1,2-cyclohexyldinitrilo tetramethylene phosphonic acid (CDTMP) as a potential bone imaging agent for positron emission tomography (PET) applications as well as to assess [188Re]-CDTMP for bone pain palliation in metastatic skeletal disorders.Methods68Ga complex of CDTMP was prepared at 80°C at pH 3.5, and 188Re complex of CDTMP was prepared at room temperature. [68Ga]-CDTMP complex was investigated as PET tracer while the therapeutic efficacy was assessed for [188Re]-CDTMP. Labeling efficiency, biodistribution, myelotoxicity, and imaging studies were carried out for the complexes synthesized. Both PET and MicroPET imaging studies were performed for [68Ga]-CDTMP whereas SPECT acquisitions were acquired for [188Re]-CDTMP. Data were analyzed semiquantitatively for all the scintigraphic scans obtained.ResultsThe radiolabeling efficiency was observed to be >70% for [68Ga]-CDTMP. High bone uptake of [68Ga]-CDTMP as compared to contralateral tissue was found in PET imaging in Balb/C mice and New Zealand rabbit; the similar result for bone uptake was correlated in the biodistribution study of the compound in BALB/c mice at different time intervals. Biodistribution experiments carried out in mice showed maximum uptake of 6.12 ± 1.22%ID/g at 45 min postinjection. For [188Re]-CDTMP, total skeletal uptake was 8.12 ± 1.11%ID/g observed at 1 h postinjection from biodistribution data. High renal uptake confirms renal route of excretion. A good hydroxyapatite binding too was seen for both the complexes. No evidence of destruction or adverse functioning of vital organs was observed for the 188Re complex.Conclusion[68Ga]-CDTMP complex can be used as a promising PET bone imaging agent and [188Re]-CDTMP as a surrogate moiety for therapeutic application. Owing to the short half-life of 68Ga (68 min), cyclotron-independent radiopharmacy, fast clearance, and rapid renal excretion as evidenced in preclinical animal models. Very low myelotoxicity and highly selective bone uptake prove the potential of [188Re]-CDTMP for therapeutic application.

show abstract

Adverse Events in the Long-Term Follow-Up of Patients Treated With Samarium Sm 153 Lexidronam for Osseous Metastases

Cited by 6 publications

References 17 publications

Beyond Palliation: Therapeutic Applications Of 153Samarium-EDTMP

Beyond Palliation: Therapeutic Applications Of 153Samarium-EDTMP

Phase I evaluation of CycloSam^® (Sm‐153‐DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma

[68Ga]/[188Re] Complexed [CDTMP] Trans-1,2-Cyclohexyldinitrilotetraphosphonic Acid As a Theranostic Agent for Skeletal Metastases

Contact Info

Product

Resources

About

Adverse Events in the Long-Term Follow-Up of Patients Treated With Samarium Sm 153 Lexidronam for Osseous Metastases

Cited by 6 publications

References 17 publications

Beyond Palliation: Therapeutic Applications Of 153Samarium-EDTMP

Beyond Palliation: Therapeutic Applications Of 153Samarium-EDTMP

Phase I evaluation of CycloSam® (Sm‐153‐DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma

[68Ga]/[188Re] Complexed [CDTMP] Trans-1,2-Cyclohexyldinitrilotetraphosphonic Acid As a Theranostic Agent for Skeletal Metastases

Contact Info

Product

Resources

About

Phase I evaluation of CycloSam^® (Sm‐153‐DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma