approved: stroke

alzheimers

dementia

epilepsy

brain death

• Tc-99m Pertechnetate

• Tc-99m DTPA

• Tc-99m Gluceptate

– I-123 Iodoamphetamine – no longer on market

– HMPAO, Tc-99m Exametazime (Ceretec)

– Tc-99m Bicisate (Neurolite)

Radiopharmaceuticals for Measuring Cerebral 

Function

• Carrier-Mediated Transport of 

Radiopharmaceuticals in the Brain

– F-18 FDG

What are the characteristics of an Ideal Cerebral Perfusion 

Agent

• High partition coefficient

• Sufficient retention within brain

• Metabolized or bound within cell

• Not trapped in lungs during first pass

• Nontoxic

• Pharmacologically inert

Cerebral Perfusion: Lipophilic 

Radiopharmaceuticals

Tc-99mExametazime

zHMPAO or Ceretec

zCrosses the BBB

zStabilized kit available

• Add 0.5 ml methylene blue to phosphate solution

• Withdraw 2 ml of blue buffer mixture

– must be used within 30 minutes

• Add 10-54 mCi TcO4- to Ceretec vial

• Add 2 ml of methylene blue stabilizer within 2 

min after adding TcO4-

• Perform Q.C. (>80%)

• Attach syringe filter for patient dose

• Use within 4 hours

QC for Ceretec

Stationary Media = ITLC-SG

solvent = MEK

Contaminant = secondary complex

location of species = origin--HR and Secondary

Solvent front--Bound and free Tc

QC for Ceretec

Stationary Media ITIC-SG

Solvent=normal saline

contaminant=free TcO4-

origin=bound, HR, and secondary

solvent front=free Tc

QC for Ceretec

Stationary Media Whatman #1

Solvent=50% acetonitrile

contaminant=HR Tc99m

Location of species = origin--HR

solvent front--bound, secondary, and free tc

• Vial A

– Bicisate (ECD)

– SnCl2

– protect from light

• Vial B

– Buffer solution

• Na Phosphate

Tc-99m Bicisate QC

%ECD=?

top

top + bottom x 100

• Acetazolamide (Diamox)

– carbonic anhydrase inhibitor

– inc. cerebral blood flow

– used to test CV hemodynamic reserve

– “stress test” for brain – works in a similar fashion 

to persantine in cardiac studies

Indium-111 DTPA

– 2.8 day T1/2

– 173 & 247 keV

– Normal dose 0.5 mCi

 Primary liver cancer is 

cancer that forms in the tissues of the liver. 

Secondary liver cancer is cancer that spreads to 

the liver from another part of the body.

Estimated new cases and deaths from liver and 

intrahepatic bile duct cancer in the United States 

in 2013:

New cases: 30,640

• Deaths: 21,670

• The percentage of Americans developing liver 

cancer has been rising slowly for several decades.

– For the treatment of patients with relapsed or 

refractory low-grade follicular, or transformed 

B-cell non-Hodgkin’s lymphoma

It is a murine monoclonal antibody 

that specifically binds to the CD20 antigen 

found on B lymphocytes.

Contraindications & 

Adverse Reactions of Bexxar 

Contraindications: Patients with know hypersensitivity to 

murine proteins or iodine.

• Adverse Reactions: 

– Possible severe infusion reactions occuring 30-120 

minutes post injection…hypotension, angioedema, hypoxia & bronchospasm (1% or less patients)

– Most adverse reactions were transient and/or reversible

– Asthenia, infection, chills, fever, headache, pain, 

nausea…

– Majority of patients experience – thrombocytopenia and neutropenia

Dosing Schedule for Bexxar

Administration

Phase 1 – Dosimetric phase – Days 1-6

– During the dosimetric phase, the patient receives a small (5mCi) dose of I-131 

Bexxar which is then used to determine the patient’s specific body dosimetry, biodistribution. This information is used to determine if the patient is a suitable candidate for the therapy and to ultimately calculated the needed therapeutic dose.

• Phase 2 – Therapeutic Phase – Days 7-14

– If the patient meets all of the criteria for 

dosing then the patient receives the 

calculated therapeutic Bexxar dose.

Dosing Schedule: Day 1-6

Dosimetric Phase

• Predosing with nonradioactive antibody –Prior to dosing with Bexxar, patient receives an IV infusion of 450 mg of nonradioactive tositumomab.

– Nonradioactive tositumomab is given prior to Bexxar to saturate circulating nonmalignant B cells to enhance the localization of Bexxar at the tumor sites.

– Following nonradioactive tositumomab administration, I-131 Bexxar 5 mCi is injected IV over 20 minutes

• Following dosimetric Bexxar dosing, patient returns 

several times for whole body dosimetry and 

biodistribution determination:

– Day 0 – Whole body dosimetry & biodistribution

– Day 2, 3 or 4 – Whole body dosimetry & 

biodistribution

– Day 6 or 7 – Whole body dosimetry & biodistribution

– Day 6 or 7 – Calculation of patient specific dose of I-

131 Bexxar to deliver 75 cGy TBD (Total Body Dose) 

for patients w/platelet counts > 150,000 OR 65 cGy

TBD for patients w/platelet counts between 100,000 –

149,000

• Prior to dosing with the therapeutic Bexxar

dose, patient receives a nonradioactive infusion 

of 450mg tositumomab.

• Following tositumomab infusion, I-131 Bexxar

therapy dose is given IV over 20 minutes.

– Patient therapy dose is based on patient 

specific dosimetry, biodistribution and 

platelet count. Normal range 100-150 mCi

– Patients w/platelet counts < 100,000 not 

eligible to receive therapy

Patients should be pretreated with SSKI, 

Lugol’s solution or potasssium iodide to 

decrease thyroid uptake. Thyroid blocking is 

begun at least 24 hours prior to the dosimetric

step and continued until 2 weeks after 

administration of the therapy dose.

• Day 1 – Blood pool, liver, spleen

• Day 2 & 3 – Less blood pool, moderate liver & 

spleen, some uptake in the renal system and 

thyroid.

Ibritumomab - Murine monoclonal antibody that specifically binds to the CD20 antigen found on B lymphocytes.

Tiuxetan - linker chelating agent that binds the monoclonal antibody (ibritumomab) to the radionuclide (either In-111 or Y-90)

Y-90 effective half-life in circulation is 30 hours. 7.2% of injected dose is excreted in urine during first 7 days post administration.

Zevalin therapy results in a sustained depletion of circulating B cells. B cell recovery begins around 12 weeks and returns to normal levels approximately 9 months following treatment.

Indium-111: 
Half-life - 2.83 days
Gamma photons - 171 & 245 keV

Yttrium-90:
Half-life - 64.1 hours
Decays by emission of beta particles to zirconium-90

Severe infusion reactions occuring 30-120 minutes post injection...hypotension, angioedema, hypoxia, & bronchospasm (1% or less patients)

Most adverse reactions were transient and/or reversible:

Asthenia, infection, chills, fever, headache, pain, nausea....

Majority of patients experience - thrombocytopenia, neutropenia, and/or anemia

Imaging Stage

Predosing with nonradioactive antibody:

Prior to dosing with Zevalin, patients receive an IV infusion of 250mg/m2 of nonradioactive Rituximab (Rituxan™)

--Rituxan is a nonradioactive murine monoclonal antibody used separately and in conjunction with Zevalin for the treatment of non-Hodgkin's lymphoma.

--Rituxan is given prior to Zevalin to saturate circulating nonmalignant B cells to enhance the localization of Zevalin at the tumor sites.

Within 4 hours of the Rituxan injection, In-111 Zevalin is injected IV over 10 minutes.

The first set of images is taken within 24 hours. The second set of images is taken at 48-72 hours post injection. A third set of optional images may be taken at 90-120 hours post injection. If biodistribution is acceptable the patients moves on to the therapeutic second phase.

Therapeutic Phase

Repeat infusion of 250mg/m2 of Rituxan

Within 4 hours Y-90 Zevalin is administered IV over 10 minutes.

Rituxan = 250mg/m2

In-111 Zevalin = 5 mCi IV over 10 min

Y-90 Zevalin = based on patient weight and platelet count:
0.4 mCi/kg for pt platelet ct > 150,000 cells/mm3

0.3 mCi/kg for pt platelet ct 100,000 - 149,000 cells/mm3

Patients with platelet ct < 100,000 not eligible to receive therapy.

Max dose = 32 mCi

One strip method using SG strip and 0.9% NaCl solvent. Bound drug stays at the origin while free Tc is isolated at the solvent front.

Bound drug purity = (cts from origin)/(cts from origin + cts from SF) X 100

USP limit = 95%