New therapies: radiation safety considerations

1. New therapies: radiation safety considerations F. Fioroni

2. Introduction Beta emitters demand other precautions than gamma emitters during preparation and administration. Beta emitters are being increasingly used for cancer treatment “old” isotopes (131I) “new” isotopes (90Y, 177Lu)

3. Beta emittersusedforradiationtherapy 131I 177Lu 90Y Half-life Radiation Mean beta energy range in water Maximum beta energy range in water range in perspex range in aluminium range in lead 8.04 d 6.71 d 64 h b-,g (100%) b-,g (17%) b- 182 keV 133 keV 933 keV 0.4 mm 0.25 mm 4.3 mm 807 keV 497 keV 2284 keV 3.6 mm 1.9 mm 11.8 mm 3.1 mm 1.6 mm 10.3 mm 1.6 mm 0.8 mm 5.2 mm 0.5 mm 0.3 mm 1.6 mm

4. ICRP 94 (International Commission on RadiologicalProtection) As iodine-131 is a frequently used high-energy gamma emitter and has an 8-day physical half-life, it results in the largest dose to medical staff, the public, and relatives after procedures involving therapeutic administration of unsealed radionuclides. Other radionuclides used in therapy are primarily beta emitters (e.g. Phosphorus-32, Strontium-89 and Yttrium-90) that pose much less risk.

5. Yttrium-90 • Half-life: 2.7 days • Emissions • (pure beta emitter) E(max)=523 keV <1% E(max) = 2284 keV 100% E(mean) = 939 keV

6. Interaction of beta particles with matter • Beta particles can give off X-rays (Bremsstrahlung) when high energy betas interact with dense shielding material Piombo Plexiglass Fractional Bremsstrahlung yield f β = 3,5 ∙ 10−4 Z Em Z = shielding atomic number Em= max energy of the beta particles

7. 90Y Shielding f β = 3,5 ∙ 10−4 Z Em Lead ( Z = 82 ) 6,5 % Plexiglas( Z ≈ 8 ) 0,64 % • Plastic or other low Z material shielding should be used to minimize exposure from Y-90. • Lead sheets or foil can be used to shield bremsstrahlung x-rays after low density shielding. Maximum Beta Range in Air: 855 cm Maximum Beta Range in Water/Tissue: 1.1 cm Maximum Beta Range in Plastic: 0.92 cm

8. Bremsstrahlungspectrum • Bremsstrahlung spectrum from a 90Y sample shielded • by 10 mm perspex. • The impact of adding 1 mm lead to the outside of the primary • perspex shielding. PMMA r values LEAD Jodal et al. Acta Oncol 2008

9. Mainpotentialriskphasesin 90Y-DOTATOC therapy Radiopharmaceuticalpreparation Patientadministration Patienthospitalization

10. 1. Radiopharmaceutical preparation Radiopharmaceutical preparation labelled with 90Y implies high exposure due to the intense field of high-energy b-particles. To keep radiation exposure as low as reasonably achievable, workers have to be correctly acquainted with the risks of exposure to b and bremsstrahlung radiation and with the use of proper protection devices. If not, local skin dose can exceed the dose limit of 500 mSv/year. The high protection standard requires:

11. Hot cell Shielding: plexiglass (1.5 cm) plus Pb (3 cm)

12. Radiation protection devices GM Survey meter to check the possible contamination of the hands.

13. Automatic dose fractionation system housed in the hot cell

14. Long tongs, PMMA cylindrical case (1-2 cm), shielded syringes (2 cm)

15. Collectionof low activitywaste < 1 uSv/h against the walls Shielded litterbin

16. Contaminated shielding storage after use < 1uSv/h After radiopharmaceutical preparation Plexiglass box

17. Dose estimation • ICRP and European Commission recommend an annual dose limit for the skin of radiation workers of 500 mSv at a depth of 70 mm averaged over any 1 cm2 regardless of the area really exposed. • In order to comply with this limit the personal dose equivalent, Hp(d), at an appropriate depth (d) in soft tissue was created as operational quantity. • For beta radiation and other weakly penetrating radiation this quantity at a depth of 0.07 mm for the skin has to be determined, denoted by Hp(0.07).

18. Dosimeters Estimation of the maximum local skin dose Hp(0.07) is performed with thin-layer ultrasensitive TLDs for soft X-rays and b radiation (LiF:Mg,Cu,P; type MCP-Ns). Thick-layerTLDs DMC 2000 XB, MGP Instr

19. Fingertips TLD dosimeters TLDs covered by anti-x and latex gloves. After each session, TLDs are collected and sent to the dosimetry laboratory.

20. Tests on anti-X gloves 90-Y source in a test tube 15.5 kcps maximum rate + 13.2 kcps maximum rate Transmission: ~ 85% 0.10 mm 11.7 kcps maximum rate + Transmission: ~75% 0.20 mm

21. Fingertip doses Chemists (1) Grassi et al. Nucl Med Commun, in press Mean handled activity 9.8 GBq/session (st. dev. 2.8 GBq /session)

22. Fingertip doses Chemists (2) Aim: to locate the critical positions and to check a potentially different behaviour of the right and left hand. No finger seems to be critically exposed because of its positioning,also due to large standard deviations

23. DOTATOC vs ZEVALIN DOTATOC Max equivalent finger dose (mSv/GBq) mSv/GBq Radiolabellingprocesses ZEVALIN mSv/GBq Radiolabellingprocesses

24. Fingertipdoses Chemists (DOTATOC vs ZEVALIN ) Left hand Right hand Left hand Right hand Doses are higher for left hand for all operators. Fingertip doses for 90Y-Zevalin labelling are on average higher than for 90Y-DOTATOC owing to the greater complexity of the procedure

25. Data comparison ASMN, Reggio Emilia IEO, Milan Cremonesi et al. Eur J Nucl Med 2006

26. A teachingaccident Radiodermatitis observed on the fingertips of an operator due to an inappropriate labelling procedure. Never touch unshielded vials, syringes directly. Cremonesi et al. Eur J Nucl Med 2006

27. Internalcontamination Inhalation of the radiopharmaceuticals was negligible, 90Y being non-volatile, differently from 131I Urine bioassay may be required for suspected skin contamination or ingestion.

28. 2. Patientadministration DOTATOC Administration vial Radiopharmaceutical is administered through an infusion system, in order to avoid the handling of syringes. Duration: between 10 and 20 minutes

29. The nuclear medicine physician TLD dosimiters Anti-X and latex gloves Anti-X apron Personal devices under and over the 0.25-mm Pb-equivalent anti-X apron

30. Physicians’ fingertip dose Doses higher than 20mSv/administration were occasionally measured during administration where some complications had arisen.

31. Anti-X apron use MGP DMC 2000 XB

32. Medical physics staff The medical physics staff usually helps chemists and physicians to correctly put on all radiation safety devices and supports the physician during patient administration. Personal equivalent doses during patient administration:

33. 3. Patient hospitalization

34. 3. Patient hospitalization Dose rate around PRRT patients after therapy. Radiation detected: Beta above 1 MeV & Gamma above 25 keV Literature data report that the dose rate close to PRRT patients drops within the first day after the treatment by more than 90% on average.

35. Radiationsafetysurveymeters Rimpler et al. Radiat Prot Dosimetry 2008 The conventionalionchamberunderestimates the real dose rate.

36. Urinaryexcretion The PRRT therapies are characterised by very rapid elimination from the body by the urine pathway. 90Y-DOTATOC 90Y- ZEVALIN:7.2% in 7 days Care must be taken to avoid possible contamination from biological fluids.

37. Tank system tocollectradioactiveexcreta

38. 177Lu • Half-time: 6.7 days • Principal Radiation Emissions: • Maximum Beta Energies 0,490 MeV • Gammas  0,208 MeV (11%) 0,113 MeV (6,4%) • Gamma constant: 7.64 nSv/hr per MBq @ 1 meter 200mCi di 177Lu:56 mSv/had 1m 10mCi di 18F:58mSv/had 1m

39. Lead ( Z = 82 ) 1,4 % Plexiglas( Z ≈ 8 ) 0,14 % 177Lu Shielding • Maximum Beta Range in Air: 135 cm • Maximum Beta Range in Water/Tissue: 1.6 mm • Half-Value Layer for Lead shielding: 0.6 mm f β = 3,5 ∙ 10−4 Z Em • Tipicalshielding: • Gammas: lead 3-5 mm • Beta:plastic 2-3 mm tissue 2 mm

40. Tests on anti-X gloves 177-Lu source in a test tube 180 cps maximum rate 340 cps maximum rate + 0.20 mm Transmission: ~189%

41. 177Lu-DOTATOC preparation (preliminary data)

42. Alfa-emitter High linear energy transfer a particles are suitable for radionuclide therapy, thanks to their radiobiological properties. They emit much higher energy particles than most of the betas, yet their ranges are two orders of magnitude lower.

43. High vs Low-LET radionuclide therapyin vitro 213 Bi-DOTATOC is significantly more potent than 177Lu-DOTATOC in vitro because of its high-LET a-emission. 213 Bi-DOTATOC shows enhanced effects on mitotic and apoptotic cell deaths. Nayak et al. Cancer Biother Radiopharm. 2005

44. Conclusion • Thanks to the physical properties of b-emitter , an increased number of therapeutic procedures is to be expected. • 90Y labelling procedures can involve higher doses to the fingers compared with typical practices in nuclear medicine. • Good laboratory practice and suitable shielding are mandatory during preparation and injection of the radioactive isotope. • Radiolabelling, administration and hospitalisation can be carried out in conditions of acceptable safety.

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