Online Resource 1: Supplemental Fig. 1, Supplemental Table 1, and Supplemental Fig. 2

(Note: Presented in the order that they are referred to in the article)

Journal Name: European Journal of Nuclear Medicine and Molecular Imaging

Article Title: Phase I pharmacokinetic and biodistribution study with escalating doses of Radium-223 dichloride in men with castration-resistant metastatic prostate cancer

Author Names and Affiliations: Jorge A. Carrasquillo1,2*, Joseph A. O’Donoghue3*, Neeta Pandit-Taskar1,2, John L. Humm3, Dana E. Rathkopf4,5, Susan F. Slovin4,5, Matthew J. Williamson3, Kristine Lacuna,4 Anne-Kirsti Aksnes6, Steven M. Larson1,2, Howard I. Scher4,5, Michael J. Morris4,5

1Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center and 2 Department of Radiology, Weill Cornell Medical College, New York, NY; 3Department of Medical Physics, Memorial Sloan-Kettering Cancer Center; 4Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; 5 Department of Medicine, Weill Cornell Medical College, New York, NY; 6Algeta ASA, Oslo, Norway.

*co first authors contributed equally to the work

Corresponding Author Information:Jorge A. Carrasquillo M.D.

Memorial Sloan-Kettering Cancer Center

1275 York Avenue

New York, NY 10065

Phone: 212-639-2459

Fax: 212-717-3263

Email:

Supplemental Fig. 1 Activity in plasma was converted to %ID/L of plasma. Mean and standard deviation were plotted at the corresponding nominal times for all patients.

Supplemental Table 1. Adverse Events on patient level (N=10 patients)

Adverse Event / Grade 1 / Grade 2 / Grade 3 / Grade 4 / Total
No. of Patients / % / No. / % / No. / % / No. / % / No. / %
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Anemia / 2 / 20% / 3 / 30% / 1 / 10% / 0 / 0% / 6 / 60%
Leukopenia / 4 / 40% / 0 / 0% / 2 / 20% / 1 / 10% / 7 / 70%
Neutropenia / 0 / 0% / 0 / 0% / 1 / 10% / 0 / 0% / 1 / 10%
Platelet count decreased / 2 / 20% / 0 / 0% / 1 / 10% / 0 / 0% / 3 / 30%
GASTROINTESTINAL DISORDERS
Diarrhea / 3 / 30% / 1 / 10% / 2 / 20% / 0 / 0% / 6 / 60%
Nausea / 2 / 20% / 2 / 20% / 1 / 10% / 0 / 0% / 5 / 50%
Vomiting / 1 / 10% / 1 / 10% / 0 / 0% / 0 / 0% / 2 / 20%
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Fatigue / 2 / 20% / 3 / 30% / 0 / 0% / 0 / 0% / 5 / 50%
INFECTIONS
Pneumonia / 0 / 0% / 0 / 0% / 0 / 0% / 1 / 10% / 1 / 10%
Urinary tract infection / 0 / 0% / 0 / 0% / 1 / 10% / 0 / 0% / 1 / 10%
INVESTIGATIONS
Blood albumin decreased / 2 / 20% / 1 / 10% / 0 / 0% / 0 / 0% / 3 / 30%
Aspartate aminotransferase increased / 0 / 0% / 0 / 0% / 1 / 10% / 0 / 0% / 1 / 10%
Blood calcium decreased / 2 / 20% / 2 / 20% / 1 / 10% / 0 / 0% / 5 / 50%
Blood creatine increased / 0 / 0% / 2 / 20% / 0 / 0% / 0 / 0% / 2 / 20%
Blood glucose increased / 3 / 30% / 1 / 10% / 0 / 0% / 0 / 0% / 4 / 40%
Blood potassium decreased / 2 / 20% / 0 / 0% / 0 / 0% / 0 / 0% / 2 / 20%
Blood sodium increased / 1 / 10% / 1 / 10% / 0 / 0% / 0 / 0% / 2 / 20%
Blood sodium decreased / 2 / 20% / 0 / 0% / 0 / 0% / 0 / 0% / 2 / 20%
Hemoglobin decreased / 1 / 10% / 1 / 10% / 0 / 0% / 0 / 0% / 2 / 20%
Blood phosphorus decreased / 0 / 0% / 2 / 20% / 0 / 0% / 0 / 0% / 2 / 20%
Blood alkaline phosphatase increased / 0 / 0% / 2 / 20% / 0 / 0% / 0 / 0% / 2 / 20%
METABOLISM AND NUTRITION DISORDERS
Anorexia / 4 / 40% / 0 / 0% / 0 / 0% / 0 / 0% / 4 / 40%
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Arthralgia / 1 / 10% / 2 / 20% / 0 / 0% / 0 / 0% / 3 / 30%
Back pain / 0 / 0% / 1 / 10% / 2 / 20% / 0 / 0% / 3 / 30%
NERVOUS SYSTEM DISORDERS
Peripheral motor neuropathy / 2 / 20% / 0 / 0% / 1 / 10% / 0 / 0% / 3 / 30%
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Dyspnea / 0 / 0% / 2 / 20% / 0 / 0% / 0 / 0% / 2 / 20%

2A 2B

2C

Supplemental Fig. 2: Waterfall plot showing: A)PSA response during treatment. PSA declines were greatest for the 2 patients at the highest doses. b) Changes in bone alkaline phosphatase response during treatment. Decline in alkaline phosphatase was seen in all patients. C) Changes in serum N-telopeptide response during treatment. Decline in serum N-telopeptide was seen 7 of 10 patients.