A Preclinical Investigation of the Saturation and Dosimetry of 153Sm-DOTMP as a Bone-Seeking Radiopharmaceutical

This paper authored by the scientists IsoTherapeutics and oncologists at M. D. Anderson Cancer Center reports that Sm-153 DOTMP(CycloSam®) has very similar dosimetry to that of Sm-153 EDTMP(Quadramet®) at low dosages. Sm-153 DOTMP appears to overcome the saturation effect that has been observed in high dose therapy with Sm-153 EDTMP, suggesting that Sm-153 DOTMP may be administered at dosages that would enable therapy with curative intent without the incommensurate elevation of the dose to the urinary system arising from the saturation effect of Sm-153 EDTMP.

Evaluation of CycloSam (Sm-153-DOTMP) as a Therapeutic Bone-Seeking Radiopharmaceutical

This poster highlights some key features of Samarium-153 DOTMP (CycloSam®). This NCI-supported research was a joint effort between scientists and oncologists from IsoTherapeutics Group, M.D. Anderson Cancer Center and the University of Missouri.  In this multi-species study that compared SM-153 DOTMP to SM-153 EDTMP (Quadramet®), myelosuppression was dramatically reduced with the use of SM-153 DOTMP, preferential skeletal uptake was optimized and no saturation effect was noted. The data showed the same drug behavior in both large and small animal models and underscored the potential for SM-153 DOTMP to be an effective therapeutic treatment for bone cancers. 

Samarium-153-DOTMP treatment of spontaneously-occurring bone cancer in dogs as a proof-of-concept model

This was a co-authored presentation between the IsoTherapeutics Group and the University of Missouri. It demonstrated the safety profile of Samarium 153 DOTMP (CycloSam®) in canines. The lack of toxicity and excellent biodistribution supports the transition to higher doses to achieve a therapeutic effect.

The Vienna protocol and perspectives in radionuclide therapy

Repeated treatments of Sm-153 EDTMP at a low dose are applied by several researchers in order to achieve the maximum therapeutic effect with the lowest hematological toxicity. Significant benefits in pain palliation, and tumor regression are documented. These results indicate the therapeutic potential of repeated low-dose Sm-153 administration in patients with bone metastasis.

Background, Reasons and Benefits Using the Vienna Protocol for the Treatment of Painful Bone Recurrences with 153Samarium-EDTMP

This paper demonstrated the effectiveness of Sm-153 in the treatment of bone metastases. In this 500-patient study, patients not only experienced effective bone pain palliation, but also improved quality of life, lesion stabilization/regression and prolonged survival. 73% showed a positive clinical response and 64% showed significant tumor regression.

Repeated low-dose Sm-153-EDTMP therapy using the Vienna protocol is effective in pain palliation and lesion regression

This presentation concludes that early and repeated dosing of Sm-153 EDTMP is the key to an improved therapeutic benefit both concerning pain palliation and lesion regression.

Radionuclidic purity aspects of 153 Sm for radionuclide therapy

Sm-153 EDTMP showed efficacy in treating bone lesions in 67% of the patients. However, some treatment limitations were noted with repeated doses due to the accumulation of the long-lived radionuclidic impurities, namely Europium, produced as a by-product of the Sm decay.

The Optimal Efficacy of a Single Therapeutic Dose of Sm-153 EDTMP in the Treatment of Painless Skeletal Metastases

Out of 103 cancer patients who received a single dose of Sm-153 EDTMP therapy, 67% showed overall therapeutic bone stabilization/regression. This study showed that Sm-153 EDTMP offers a riskless and effective therapy option in patients with painful bone disseminations, it also provides encouraging results among those with painless skeletal metastases.

Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases

This paper analyzes 91 phosphonate-based radiopharmaceuticals based on systematic literature and review. The paper outlines in a table the “Key Characteristics” of bone targeting radiopharmaceuticals based on the extensive review of papers. These criteria not only include efficacy but also the ability to manufacture as well as convenience and most importantly a short half-life which allows for repeats dosing. Samarium 153 DOTMP (CycloSam®) was the only radiopharmaceutical to meet all of the criteria listed.

Dosimetric implications of the potential radionuclidic impurities in 153Sm-DOTMP

In this paper, the human internal dosimetry of the radionuclidic impurities of Samarium-153 in Samarium153-DOTMP(CycloSam®), has been estimated from preclinical data. It was concluded that the effective dose from the radionuclidic impurities in the lower-specific-activity 153Sm that is used to make 153Sm-DOTMP is a small fraction of the overall effective dose.