Download What`s New and on the Horizon in Radiopharmaceuticals

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