Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy.

INTRODUCTION: Since the prostate-specific membrane antigen (PSMA) is frequently over-expressed in prostate cancer (PCa) several PSMA-targeting molecules are under development to detect and treat metastatic castration resistant prostate cancer (mCRPC). We investigated the tissue kinetics of a small molecule inhibitor of PSMA ((S)-2-(3-((S)-1-carboxy-5-(3-(4-[(124)I]iodophenyl)ureido)pentyl)ureido)pentanedioicacid; MIP-1095) using PET/CT to estimate radiation dosimetry for the potential therapeutic use of (131)I-MIP-1095 in men with mCRPC. We also report preliminary safety and efficacy of the first 28 consecutive patients treated under a compassionate-use protocol with a single cycle of (131)I-MIP-1095. METHODS: Sixteen patients with known prostate cancer underwent PET/CT imaging after i.v. administration of (124)I-MIP-1095 (mean activity: 67.4 MBq). Each patient was scanned using PET/CT up to five times at 1, 4, 24, 48 and 72 h post injection. Volumes of interest were defined for tumor lesions and normal organs at each time point followed by dose calculations using the OLINDA/EXM software. Twenty-eight men with mCRPC were treated with a single cycle of (131)I-MIP-1095 (mean activity: 4.8 GBq, range 2 to 7.2 GBq) and followed for safety and efficacy. Baseline and follow up examinations included a complete blood count, liver and kidney function tests, and measurement of serum PSA. RESULTS: I-124-MIP-1095 PET/CT images showed excellent tumor uptake and moderate uptake in liver, proximal intestine and within a few hours post-injection also in the kidneys. High uptake values were observed only in salivary and lacrimal glands. Dosimetry estimates for I-131-MIP-1095 revealed that the highest absorbed doses were delivered to the salivary glands (3.8 mSv/MBq, liver (1.7 mSv/MBq) and kidneys (1.4 mSv/MBq). The absorbed dose calculated for the red marrow was 0.37 mSv/MBq. PSA values decreased by >50 % in 60.7 % of the men treated. Of men with bone pain, 84.6 % showed complete or moderate reduction in pain. Hematological toxicities were mild. Of men treated, 25 % had a transient slight to moderate dry mouth. No adverse effects on renal function were observed. CONCLUSION: Based on the biodistribution and dose calculations of the PSMA-targeted small molecule (124)I-MIP-1095 therapy with the authentic analog (131)I-MIP-1095 enables a targeted tumor therapy with unprecedented doses delivered to the tumor lesions. Involved lymph node and bone metastases were exposed to estimated absorbed doses upwards of 300 Gy.

Iodofiltic acid I 123 (BMIPP) fatty acid imaging improves initial diagnosis in emergency department patients with suspected acute coronary syndromes: a multicenter trial.

OBJECTIVES: The aim of this study was to assess the performance of beta-methyl-p-[123I]-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) to detect acute coronary syndromes (ACS) in emergency department patients with chest pain. BACKGROUND: Emergency department diagnosis of chest pain is problematic, often requiring prolonged observation and stress testing. BMIPP SPECT detects abnormalities in fatty acid metabolism resulting from myocardial ischemia, even many hours after symptom cessation. METHODS: Emergency department patients with suspected ACS were enrolled at 50 centers. Patients received 5 mCi BMIPP within 30 h of symptom cessation. BMIPP SPECT images were interpreted semiquantitatively by 3 blinded readers. Initial clinical diagnosis was based on symptoms, initial electrocardiograms, and troponin, whereas the final diagnosis was based on all available data (including angiography and stress SPECT) but not BMIPP SPECT. Final diagnoses were adjudicated by a blinded committee as ACS, intermediate likelihood of ACS, or negative for ACS. RESULTS: A total of 507 patients were studied and efficacy was evaluated in 448 patients with sufficient data. The sensitivity of BMIPP by 3 blinded readers for a final diagnosis of ACS and intermediate likelihood of ACS was 71% (95% confidence interval [CI]: 64% to 79%), 74% (95% CI: 68% to 81%), and 69% (95% CI: 62% to 77%); the corresponding specificity of BMIPP was 67% (95% CI: 61% to 73%), 54% (95% CI: 48% to 60%), and 70% (95% CI: 64% to 76%). Compared with the initial diagnosis alone, BMIPP+initial diagnosis increased sensitivity from 43% to 81% (p<0.001), negative predictive value from 62% to 83% (p<0.001), and positive predictive value from 41% to 58% (p<0.001), whereas specificity was unchanged (61% to 62%, p=NS). CONCLUSIONS: The addition of BMIPP data to the initially available clinical information adds incremental value toward the early diagnosis of an ACS, potentially allowing determination of the presence or absence of ACS to be made earlier in the evaluation process. (Safety and Efficacy Iodofiltic Acid I 123 in the Treatment of Acute Coronary Syndrome [Zeus-ACS]; NCT00514501).