Production, biodistribution assessment and dosimetric evaluation of 177Lu-TTHMP as a bone pain palliation agent

Document Type: Original Article

Authors

Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran

10.7508/aojnmb.2015.01.006

Abstract

Objective(s): Recently, bone-avid radiopharmaceuticals have been shown to have potential benefits for the treatment of widespread bone metastases. Although 177Lutriethylene tetramine hexa methylene phosphonic acid (abbreviated as 177Lu- TTHMP), as an agent for bone pain palliation, has been evaluated in previous studies, there are large discrepancies between the obtained results. In this study, production, quality control, biodistribution, and dose evaluation of 177Lu-TTHMP have been investigated and compared with the previously reported data.
Methods: TTHMP was synthesized and characterized, using spectroscopic methods. Radiochemical purity of the 177Lu-TTHMP complex was determined using instant thin-layer chromatography (ITLC) and high performance liquid chromatography (HPLC) methods. The complex was injected to wild-type rats and biodistribution was studied for 7 days. Preliminary dose evaluation was investigated based on
biodistribution data in rats.
Results: 177Lu was prepared with 2.6-3 GBq/mg specific activity and radionuclide purity of 99.98%. 177Lu-TTHMP was successfully prepared with high radiochemical purity (>99%). The complex showed rapid bone uptake, while accumulation in other organs was insignificant. Dosimetric results showed that all tissues received almost insignificant absorbed doses in comparison with bone tissues.
Conclusion: Based on the obtained results, this radiopharmaceutical can be a good candidate for bone pain palliation therapy in skeletal metastases.

Keywords

Main Subjects


1. Serafini AN. Therapy of metastatic bone pain. J Nucl Med. 2001;42:895-906.

2. Pandit-Taskar N, Batraki M, Divgi CR. Radiopharmaceutical Therapy for Palliation of Bone Pain from Osseous Metastases. J Nucl Med. 2004; 45:1358–65.

3. Criteria for Palliation of Bone Metastases –Clinical Applications, IAEA-TECDOC-1549. Austria, Vienna: IAEA; 2007.

4. Lipton A. Pathophysiology of Bone Metastases: How This Knowledge May Lead to Therapeutic Intervention. J Support Oncol. 2004; 2:205-13.

5. Liberman B, Gianfelice D, Inbar Y, Beck A, Rabin T, Shabshin N, et al. Pain Palliation in Patients with Bone Metastases Using MR-Guided Focused Ultrasound Surgery: A Multicenter Study. Ann Surg Oncol. 2009; 16:140-6.

6. Rajendran JG, Eary JF, Bensinger W, Durack LD, Vernon C, Fritzberg A. High-Dose 166Ho-DOTMP in Myeloablative Treatment of Multiple Myeloma: Pharmacokinetics, Biodistribution, and Absorbed Dose Estimation. J Nucl Med. 2002; 43:1383-90.

7. Farhanghi M, Holmes RA, Volkert WA, Logan KW, Singh A. Samarium- 153-EDTMP: Pharmacokinetic, Toxicity and Pain Response Using an Escalating Dose Schedule in Treatment of Metastatic Bone Cancer. J NucI Med. 1992; 33:1451-8.

8. Hosain F, Spencer RP. Radiopharmaceuticals for palliation of metastatic osseous lesions: biologic and physical background. Semin Nucl Med. 1992; 22:11–6.

9. Deligny CL, Gelsema WJ, Tji TG, Huigen YM, Vink HA. Bone seeking radiopharmaceuticals. Nucl Med Biol. 1990; 17:161 179.

10. Lewington VJ. Targeted radionuclide therapy for bone metastases. Eur J Nucl Med. 1993; 20:66-74.

11. Breitz H, Wendt R, Stabin M, Bouchet L, Wessels B. Dosimetry of high dose skeletal targeted radiotherapy (STR) with 177Lu-DOTMP. Cancer Biother Radiopharm. 2003; 18:225-30.

12. Bahrami-Samani A, Anvari A, Jalilian AR, Shirvani-Arani S, Yousefnia H, Aghamiri MR, et al. Production, quality control and pharmacokinetic studies of 177Lu-EDTMP for human bone pain palliation therapy trials. Iran J Pharmaceut Res. 2012; 11:137-44.

13. Abbasi IA. Preliminary studies on 177Lu-labeled sodium pyrophosphate (177Lu-PYP) as a potential bone-seeking radiopharmaceutical for bone pain palliation. Nucl Med Biol. 2012; 39:763-9.

14. Chakraborty S, Das T, Unni PR, Sarma HD, Samuel G, Banerjee S, et al. 177Lu labeled polyaminophosphonates as potential agents for bone pain palliation. Nucl Med Commun. 2002; 23: 67-74.

15. Abbasi IA. Studies on 177Lu-labeled methylene diphosphonate as potential bone-seeking radiopharmaceutical for bone pain palliation. Nucl Med Biol. 2011; 38:417–25.

16. Lungu V, Niculae D, Bouziotis P, Pirmettis I, Podina C. Radiolabeled phosphonates for bone metastases therapy. J Radioanalytical Nucl Chem. 2007; 273:663–7.

17. Das T, Chakraborty S, Unni PR, Banerjee S, Samuel G, Sarma HD, et al. 177Lu-labeled cyclic polyaminophosphonates as potential agents for bone pain palliation. Appl Radiat Isotopes. 2002; 57:177–84.

18. Manual For Reactor Produced Radioisotopes, IAEA-TECDOC-1340. Austria, Vienna: IAEA; 2003.

19. Sparks RB, Aydogan B. Comparison of the effectiveness of some common animal data scaling techniques in estimating human radiation dose. Proceeding of the sixth International Radiopharmaceutical Dosimetry Symposium; Oak Ridge. TN: Oak Ridge Associated Universities; 1996. pp. 705–16.

20. Bevelacqua JJ. Internal Dosimetry Primer. Radiat Prot Manage. 2005; 22:7-17.

21. OLINDA - Organ Level Internal Dose Assessment Code (Version 1.1), copyright Vanderbilt University; 2007.

22. Mitterhauser M, Toegel S. What to consider in the development of new bone seekers: mechanistic and tracer-related aspects. Nucl Med Biol. 2008; 35:817–24.