99mTc-MIP-1404 for Imaging Prostate Cancer: Phase I Clinical Study to Assess the Image Quality of a Simplified Kit Formulation Compared to a Multi-step Preparation of 99mTc-MIP-1404

This trial is a single-blind, cross-over design. Up to three patients with confirmed metastatic prostate adenocarcinoma and up to three healthy volunteers will receive two doses of 20.0 (± 3) mCi of intravenously administered 99mTc MIP 1404 (preparation A or preparation B). Whole-body planar scintigraphic images will be acquired at various time points on the day of study drug administration. A pelvic SPECT/CT image will be acquired on the day of study drug administration. Blood will be collected for pharmacokinetic measurements following study drug administration. Each participant will receive an initial study drug administration (preparation A) and a second study drug administration (preparation B) approximately 7 to 21 days later. A final follow-up visit will occur approximately 2 - 3 weeks after the second study drug administration.

• Experimental: Preparation A
  20 (±3) mCi 99mTc-MIP-1404 (preparation A)
  Intervention: Drug: 99mTc-MIP-1404
• Experimental: Preparation B
  20 (±3) mCi 99mTc-MIP-1404 (preparation B)
  Intervention: Drug: 99mTc-MIP-1404

• Pinto JT, Suffoletto BP, Berzin TM, Qiao CH, Lin S, Tong WP, May F, Mukherjee B, Heston WD. Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells. Clin Cancer Res. 1996 Sep;2(9):1445-51.
• Smith-Jones PM, Vallabahajosula S, Goldsmith SJ, Navarro V, Hunter CJ, Bastidas D, Bander NH. In vitro characterization of radiolabeled monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen. Cancer Res. 2000 Sep 15;60(18):5237-43.
• Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004 Feb 15;91(3):528-39. Review.
• Kinoshita Y, Kuratsukuri K, Landas S, Imaida K, Rovito PM Jr, Wang CY, Haas GP. Expression of prostate-specific membrane antigen in normal and malignant human tissues. World J Surg. 2006 Apr;30(4):628-36.
• Murphy GP, Elgamal AA, Su SL, Bostwick DG, Holmes EH. Current evaluation of the tissue localization and diagnostic utility of prostate specific membrane antigen. Cancer. 1998 Dec 1;83(11):2259-69. Review.
• Vallabhajosula S, Kuji I, Hamacher KA, Konishi S, Kostakoglu L, Kothari PA, Milowski MI, Nanus DM, Bander NH, Goldsmith SJ. Pharmacokinetics and biodistribution of 111In- and 177Lu-labeled J591 antibody specific for prostate-specific membrane antigen: prediction of 90Y-J591 radiation dosimetry based on 111In or 177Lu? J Nucl Med. 2005 Apr;46(4):634-41.
• Olson WC, Heston WD, Rajasekaran AK. Clinical trials of cancer therapies targeting prostate-specific membrane antigen. Rev Recent Clin Trials. 2007 Sep;2(3):182-90. Review.
• Rajasekaran AK, Anilkumar G, Christiansen JJ. Is prostate-specific membrane antigen a multifunctional protein? Am J Physiol Cell Physiol. 2005 May;288(5):C975-81. Review.
• Slovin SF. Targeting novel antigens for prostate cancer treatment: focus on prostate-specific membrane antigen. Expert Opin Ther Targets. 2005 Jun;9(3):561-70. Review.
• Barrett PH, Bell BM, Cobelli C, Golde H, Schumitzky A, Vicini P, Foster DM. SAAM II: Simulation, Analysis, and Modeling Software for tracer and pharmacokinetic studies. Metabolism. 1998 Apr;47(4):484-92.
• Stabin MG, Siegel JA. Physical models and dose factors for use in internal dose assessment. Health Phys. 2003 Sep;85(3):294-310.
• Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005 Jun;46(6):1023-7.
• Pan ZY, Wolf W. Computer package for the calculation of the radiation dose to patients, based on the MIRD approach. J Nucl Med. 1985 Mar;26(3):318-20.

Inclusion Criteria:

• Male aged 21 years or older.
• Ability to provide signed informed consent and willingness to comply with protocol requirements.
• Participants must agree to use an acceptable form of birth control throughout the study period. Participants must agree to use condoms for a period of seven days after each study drug administration, if engaged in sexual activity.

Additional Inclusion Criteria for Metastatic Prostate Adenocarcinoma Patients:

• Histologic diagnosis of prostate cancer by validated medical history (pathology report, if available).
• Evidence of metastatic disease demonstrated by a documented abnormal bone scan, CT scan, or MRI
• Karnofsky performance is ≥ 60

Additional Inclusion Criteria for Healthy Volunteers:

• PSA laboratory assessment within normal range (PSA < 4 ng/ml)
• Normal findings on a digital rectal examination
• Hemoglobin and hematocrit within normal range

Exclusion Criteria:

• Received a radioisotope within 5 physical half lives of that radioisotope prior to study enrollment
• Have any medical condition or other circumstances which, in the opinion of the Investigator, would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or post dose follow-up examinations
• Participant is determined by the Investigator to be clinically unsuitable for the study
• Serum creatinine ≥ 2.0 mg/dl
• Total bilirubin ≥ 2.0 mg/dl
• Liver transaminases ≥ 1.5 x ULN
• Platelet count < 100,000/mm3
• Absolute neutrophil count (ANC) < 2,000/mm3
• Hematocrit < 30% or hemoglobin < 10 g/dl

Additional Exclusion Criteria for Metastatic Prostate Adenocarcinoma Patients:

• Have received a permanent prostate brachytherapy implant within the last 3 months for 103Pd implants; or 12 months for 125I implants
• Have had any other malignancies within the past year, other than basal or squamous cell carcinoma of the skin, in which the diagnosis and location have not been defined as clinically controlled or treated to complete response