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What’s New and on the Horizon in Radiopharmaceuticals Nicki Hilliard, PharmD Nicki Hilliard, PharmD, BCNP University of Arkansas for Medical Sciences Brain Imaging Beta Amyloid Agents Brain Imaging Facts about Alzheimer’s Disease 20% of people diagnosed with Alzheimer’s do not have disease Alzheimer’s Disease Mortality Brain Imaging Beta Amyloid AB Beta Amyloid Imaging Appropriate Use Appropriate Candidates 1. Those who complain of persistent or progressive unexplained memory problems or confusion and who demonstrate impairments using standard tests of cognition and memory. 2. Individuals meeting tests for possible Alzheimer's, but who are unusual in their clinical presentation. 3. Individuals with progressive dementia and atypically early age of onset (before age 65). Amyloid Imaging Task Force Recommendations Beta Amyloid Imaging Appropriate Use Inappropriate Candidates 1. Those who are age 65 or older and meet standard definitions and tests for Alzheimer's, since a positive PET scan would provide little added value. 1. Asymptomatic people or those with a cognitive complaint but no clinical confirmation of impairment. Beta Amyloid Imaging Lack of Reimbursement “We will cover one PET AB scan per patient through coverage with evidence development (CED).” Brain Imaging Lack of Reimbursement Beta Amyloid Imaging F-18 Florbetapir- Amyvid • Only sure diagnosis has been autopsy • Based C-11 Pittsburgh Compound • Avid Eli Lilly • Compared PET images to autopsy results • FDA approved January 2011 • Used to evaluate Alzheimer’s drug therapy Beta Amyloid Imaging F-18 Florbetapir- Amyvid NEGATIVE AMYVID PET SCAN POSITIVE AMYVID PET SCAN http:// Beta Amyloid Imaging F-18 Florbetapir- Amyvid Brain Imaging F-18 Flutemetamol - Vizamyl Image: http://www.alzforum.orgt Beta Amyloid Imaging More in development Generic Trade F-18 Florbetaben NeuroCeq F-18 NAV4694 Manufacturer Piramal Imaging (IBA) Navidea Brain Imaging Lack of Reimbursement Help us! We need a cure! We want Nuclear Medicine Cancer Imaging Lymphatic Mapping Tc-99m Tilmanocept Indications >206,000 >61,000 Sentinel Node Imaging Cancer Staging Melanoma Survival Rates IA 97% IIA 81% IIIA 78% IV 15-20% Lower for States B & C Mechanism of Action Tc99m Tilmanocept Activity & Volume Activity: 0.5 mCi Volume: • • • 0.1 ml administered in a single syringe; 0.5 ml administered in a single syringe or in multiple syringes (0.1 ml to 0.25 ml each) 1 ml administered in multiple syringes (0.2 ml to 0.5 ml each) Tc99m Tilmanocept Imaging Time MINUTES HOURS Tc99m Tilmanocept Drug Interaction Lidocaine slows lymphatic drainage Do not pre-administer Do not add to syringe Tc99m Tilmanocept Injection Breast cancer: 1. Intradermal 2. Subcutaneous, 3. Subareolar 4. Peritumoral Melanoma: 1. Intradermal 2. Subcutaneous Pain Tc99m Tilmanocept Availability Manufacturer: Navidea Biopharmaceuticals Distributor: Cardinal Health Cost: ~$300 per patient 1 vial sufficient for up to 4 patient doses Cancer Therapy Prostate Cancer Therapy Prostate Cancer Therapy Facts about Prostate Cancer 238,590 Men diagnosed with Prostate cancer in 2013 29,790 Prostate cancer deaths Prostate Cancer C-11 Choline Radium-223 Radium 223 Alpha Emission T1/2 = 15.4 days 28 MeV 95.3% alphas 3.6% betas 1.1 % gamma or X-rays Alpha range of 2-10 cell diameters Radium-223 Mechanism of Action Clinical trials ongoing for uses in Multiple Myeloma, Osteosarcoma,& Breast Cancer Radium-223 Increased Survival Radium-223 Manufacturer / Marketing Radium-223 Dose 1.35 uCi / kg 4 week intervals x 6 Slow IV injection over 1 min Radium-223 Volume to be administered Body wt in kg / 1.35 uCi/kg Decay factor x 27 uCi/ ml Radium-223 Hematological Evaluation Blood Counts: Baseline and prior to each dose ANC > 1.5 x 109 Platelets >100 x 109 Hemoglobin >10 g/dL Radium-223 Hematological Evaluation Radium-223 Adverse Reactions >10% Peripheral edema (13%) Diarrhea (25%) Nausea (36%) Vomiting (19%) Anemia (93%) Lymphocytopenia (72%) Leukopenia (35%) Thrombocytopenia (31%) Neutropenia (18%) 1-10% Dehydration Pancytopenia Renal failure/insufficiency Injection site reactions (erythema, pain, swelling) <1% Aplastic anemia Radium-223 Costs $69,000 6 injections Prostate Cancer Investigational New RPs for Prostate Cancer F-18 Flucyclidine Measures the metabolism of amino acids in tumors and indicates amino acid synthesis. Sensitive indicator of tumor growth for prostate cancer where glucose metabolism is too slow for FDG imaging. Lu-177 Capromab Phase II study of radiolabeled prostate specific membrane antigen (PSMA) for prostate cancer therapy. Neuroendocrine Tumors Ga-68 and Y-90 DOTATOC Cardiac Imaging New Indications Heart Failure I-123 MIBG (AdreView) Cardiac Indication: • assessment of sympathetic innervation of the myocardium by measurement of the heart to mediastinum (H/M) ratio of radioactivity uptake in patients with New York Heart Association (NYHA) class II or class III heart failure and left ventricular ejection fraction (LVEF) ≤ 35%. Among these patients, I-123 MIBG may be used to help identify patients with lower one and two year mortality risks, as indicated by an H/M ratio ≥ 1.6. Heart Failure Mechanism of Action Taken up by the NE transporter in adrenergic nerve terminals and stored in the presynaptic storage vesicles I-131 MIBG Accumulates in adrenal medulla, salivary glands, heart, liver, spleen, lungs and neural crest tumors. Norepinephrine MIBG Heart Failure I-123 MIBG (AdreView) Heart Failure Normal HMR: 1.80 Decreased MIBG activity 1.10 I-123 MIBG Dose and Precautions Administer thyroid blockade medications SSKI /Lugol’s – 100 mg iodine 1 hr before I-123 MIBG Interactions Drugs Mechanism of Interference Withdraw Prior Opioids, Cocaine, Tramadol Uptake inhibition 7-14 days Tricyclic antidepressants (Amitriptyline and deriv., imipramine and derv., amoxapine, others) Uptake inhibition 7-21 days Sympathicomimetics (Phenylopropanolamine, psuedoephedrine, phenilephrine, amphetamine, dopamine, isoproperenol Depletion of granules 7-14 days Labetalol, metoprolol, amiodarone Inhibition of uptake and depletion 21 days Reserpine Depletion and transport inhibition 14 days Amlodipine Increased uptake and retention 14 days Captopril, enalapril Increased uptake and retention 14 days Phenothiazines Uptake inhibition 21-28 days Thioxanthenes Uptake inhibition 21-28 days Cardiac PET F-18 Flurpiridaz F-18 Flurpiridaz Phase 3 Cardiac Imaging Investigational New RPs F-18 BFPET Myocardial perfusion agent that concentrates in healthy myocardial cells F-18 CardioPET Myocardial uptake of the heart’s primary source of energy, fatty acids. Can measure perfusion initially, then determine tissue viability to diagnose acute coronary syndrome and CAD. Can evaluate CAD in patients that cannot exercise, F-18 VasoPET Agent accumulates in inflammation and identifies vulnerable plaques, promising the means to assess the degree of risk patients may be at for stroke or heart attack. Navidea Pipeline Slides Available