George Sgouros, Ph.D.

Russell H. Morgan Dept of Radiology & Radiological Science

Johns Hopkins University, School of MedicineBaltimore MD

Bismuth-213

Disclosures

Consultant: Bayer, Roche, RadiomedixScientific Advisory Board: Orano MedFounder: Radiopharmaceutical Imaging and

Dosimetry (RAPID), LLC

Antibody Targeting - Solid Disease

extra-vasation

Y Y

diffusion

penetration

Antibody Targeting - Micrometastases

Y

penetration

Antibody Targeting - Leukemia

Y

83Bi213

(2.2%)

45.6 m

0.16% 5.5 MeV2.01% 5.9 MeV

α

81Tl209

2.2 m

82Pb209

3.25 h

84Po213

4.2 µs

αβ-

β-(97.8%)

8.4 MeV

β-

83Bi209

> 1019 yr

Bi-213 Decay Scheme

213Bi-HuM195 Leukemia Trial• Rapid (5-10 min) targeting of disease

- 45.6 min half-life is not limiting• Marrow toxicity (nadir duration) similar to 90Y • Targeting of rapidly accessible disease

- micrometastases

Short Time Scale • Inject under a gamma camera

- Collect in dynamic or list mode- SPECT imaging may not be feasible- Image over critical tissues

• Feasibility of biopsy, tissue sampling

• Relevance of biological clearance

Bi-213 Decay CharacteristicsALPHA PARTICLES

isotope effective delta deltaenergy % per % per (Gy-kg/ (g-rad/

ISOTOPE (keV) disin. disin. (kev/dis) Bq-s) µCi-hr)Bi-213 5549 0.16 0.16 8.88 1.42E-15 .019Bi-213 5869 2.01 2.01 117.97 1.89E-14 .252Po-213 7614 0.00 0.00 0.22 3.58E-17 .000Po-213 8375 100.00 97.80 8190.75 1.31E-12 17.472

SUM 8318 1.33E-12 17.743

Sgouros, et al. JNM ‘99

Bi-213 Decay Characteristics

Sgouros, et al. JNM ‘99

Bi-213 Decay Characteristics

Sgouros, et al. JNM ‘99

• 213Bi decays are confined to blood- apportion decays according to each tissues blood volume

- alphas have a range of 60-90 microns and do not irradiate normal tissue

- electrons have a range of 5 to 10 mm and could irradiate normal tissue even if they originate in the vasculature

• 209Pb rapidly extravasates- Electron range is 0.5 to 1 mm

• 209Pb is confined to blood- Complexed with hemoglobin and remains in red blood cell compartment

Distribution assumptions for normal tissues

Where/how to distribute energy? • Absorbed dose = energy absorbed in

volume/volume mass

• Total alpha, electron and photon energy emitted by parent and daughters

• Use range, half-life, likely biologic fate of daughter in deciding apportionment

60-90 µm

alphas

60-90 µm× 100

213Bi-electrons

60-90 µm× 10

209Pb-electrons

RBC-bound free

Distribution assumptions for normal tissues

(not drawn to scale)

In-111 Day 4, posterior Bi-213, 4th inj., summed posterior

HuM195 (anti-CD33)

Sgouros, et al. JNM ‘99

HuM195 (anti-CD33)

Sgouros, et al. JNM ‘99

Dosimetry - results

Sgouros, et al. JNM ‘99

213Bi-HuM195 Leukemia Trial Marrow

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Sgouros, et al. JNM ‘99

AcknowledgmentsÅse BallangrudWei-Hong YangKlaus HamacherKatherine Kolbert

Sherry Farzan-KashaniRobert DenJessica Loh

David ScheinbergMichael McDevittDangshe MaJoe Jurcic

Ron Finn

C. Clifton Ling

Steven Larson

John Humm

Joseph O'Donoghue

Slide Number 1DisclosuresAntibody Targeting - Solid DiseaseAntibody Targeting - MicrometastasesAntibody Targeting - LeukemiaBi-213 Decay Scheme213Bi-HuM195 Leukemia TrialSlide Number 8Bi-213 Decay CharacteristicsBi-213 Decay CharacteristicsBi-213 Decay CharacteristicsSlide Number 12Where/how to distribute energy? Slide Number 14Slide Number 15Slide Number 16Dosimetry - results213Bi-HuM195 Leukemia Trial Slide Number 19Acknowledgments