Radiopharmaceuticals and Dosages Review

Radiopharmaceuticals and Dosages

• Gastroesophageal Reflux Study

  • Radiopharmaceutical: Tc99m Sulfur Colloid
  • Dose: 300 uCi mixed with 150 mL of 0.1 N hydrochloric acid and 150 mL of orange juice

• Solid Gastric Emptying

  • Radiopharmaceutical: Tc99m Sulfur Colloid
  • Dose: 0.5-1 mCi mixed with eggs

• Liquid Gastric Emptying

  • Radiopharmaceutical: In-111 DTPA
  • Dose: 75 uCi in water

• GI Bleed Study

  • Radiopharmaceutical: Tc99m RBCs
  • Dose: 20-30 mCi

• Meckel's Diverticulum

  • Radiopharmaceutical: TcO4 - (Pertechnetate)
  • Pediatric Dose: 200-300 uCi/kg
  • Adult Dose: 10-15 mCi

• Liver-Spleen Scan

  • Radiopharmaceutical: Tc99m Sulfur Colloid
  • Dose: 5-10 mCi

• Liver Hemangioma Scan

  • Radiopharmaceutical: Tc99m RBCs
  • Dose: 15-25 mCi

• Hepatobiliary Scan

  • Radiopharmaceuticals: Tc99m Mebrofenin, Tc99m Disofenin
  • Dose: 1-5 mCi

• LeVeen Shunt Study

  • Radiopharmaceuticals: Tc99m MAA, Tc99m Sulfur Colloid
  • Dose: 5 mCi

• Brain Death Study

  • Radiopharmaceuticals: Tc99m ECD, Tc99m HMPAO
  • Dose: 10-20 mCi

• PET Brain Study

  • Radiopharmaceutical: F18 FDG
  • Dose: 10-20 mCi

• Brain Tumors Imaging

  • Radiopharmaceuticals: F18 FDG or Tl-201 alongside Tc99m Sestamibi
  • Dose: 10-20 mCi (FDG)

• Beta Amyloid Plaque Imaging for Alzheimer's Disease

  • Radiopharmaceuticals: F18 Florbetapir, F18 Flutemetamol, F18 Florbetaben
  • Doses: 10 mCi, 5 mCi, 8 mCi respectively

• Tau Imaging for Alzheimer's Disease

  • Radiopharmaceutical: F18 Flortaucipir
  • Dose: 10 mCi

• Parkinsonian Imaging

  • Radiopharmaceuticals: I-123 Ioflupane, F18 Fluorodopa
  • Doses: 3-5 mCi, 5 mCi respectively

• Cisternogram for Hydrocephalus

  • Radiopharmaceutical: In-111 DTPA
  • Dose: 500 uCi

• CSF Shunt Study

  • Radiopharmaceuticals: In-111 DTPA, Tc99m DTPA
  • Doses: 0.5 mCi, 1-3 mCi respectively

• CSF Leak Study

  • Radiopharmaceutical: In-111 DTPA
  • Dose: 0.5 mCi

• Renogram with Lasix

  • Radiopharmaceuticals: Tc99m MAG3, Tc99m DTPA
  • Doses: 10 mCi

• Morphological Renal Imaging

  • Radiopharmaceuticals: Tc99m DMSA, Tc99m Glucoheptonate
  • Doses: 1-6 mCi, 10-20 mCi respectively

• Renogram with Captopril (2 Stage)

  • Radiopharmaceutical: Tc99m MAG3
  • Dosage for baseline: 1-2 mCi and for Captopril image: 10 mCi

• Renogram with Captopril (1 Stage)

  • Radiopharmaceutical: Tc99m MAG3
  • Dose: 10 mCi

• PET Bone Scan

  • Radiopharmaceutical: F18 NaF
  • Dose: 5-10 mCi

• Bone Scan

  • Radiopharmaceutical: Tc99m MDP
  • Dose: 10-20 mCi

• 3-Phase Bone Scan

  • Radiopharmaceutical: Tc99m MDP
  • Dose: 10-20 mCi

• Bone Pain Palliative Therapy

  • Radiopharmaceuticals: Sr-89 Chloride, Sm-153 EDTMP
  • Doses: 4 mCi (40-60 uCi/kg), 1.0 mCi/kg respectively

• mCRPC Therapy

  • Radiopharmaceutical: Ra-223 Dichloride
  • Dose: 1.49 uCi/kg at 4 week intervals for 6 injections

• Bone Marrow Scan

  • Radiopharmaceutical: Tc99m Sulfur Colloid
  • Dose: 10-15 mCi

• Lung Perfusion Scan

  • Radiopharmaceutical: Tc99m MAA
  • Dose: 1-4 mCi

• Lung Ventilation Scan

  • Radiopharmaceuticals: Xe-133 Gas, Tc99m DTPA (aerosol)
  • Doses: 10-20 mCi, 25-40 mCi respectively

• General PET Oncology

  • Radiopharmaceutical: F18 FDG
  • Dose: 10-15 mCi

• Thyroid Uptake/Scan

  • Radiopharmaceuticals: I-131 Sodium Iodide, I-123 Sodium Iodide, TcO4 - (Pertechnetate)
  • Doses: 5-30 uCi, 200-400 uCi, 2-10 mCi (scan only)

• Thyroid Uptake Only

  • Radiopharmaceutical: I-123 Sodium Iodide
  • Dose: 50-100 uCi

• Pre-Therapy Thyroid Scan

  • Radiopharmaceutical: I-131 Sodium Iodide
  • Dose: 1-5 mCi

• Thyroid Therapy

  • Radiopharmaceutical: I-131 Sodium Iodide
  • Doses: 30-100 mCi (ablate), 150-200 mCi (local mets), 200-300 mCi (distant mets)

• Dual Isotope Parathyroid Scan

  • Radiopharmaceuticals: TcO4 - (Pertechnetate), Tc99m Sestamibi
  • Doses: 4-6 mCi, 20-25 mCi respectively

• Dual Phase Parathyroid Scan

  • Radiopharmaceutical: Tc99m Sestamibi
  • Dose: 10-20 mCi

• Neuroendocrine Tumor Scan

  • Radiopharmaceutical: In-111 DTPA Octreotide
  • Dose: 6 mCi

• Pheochromocytoma Scan

  • Radiopharmaceuticals: I-131 MIBG, I-123 MIBG
  • Doses: 0.5-1 mCi, 3-10 mCi respectively

• Vesicoureteral Reflux Study (Direct)

  • Radiopharmaceuticals: TcO4 - (Pertechnetate), Tc99m Sulfur Colloid, Tc99m DTPA
  • Dose: 0.5-1 mCi in appropriate amount of saline to fill bladder

• Vesicoureteral Reflux Study (Indirect)

  • Radiopharmaceutical: Tc99m DTPA
  • Dose: ???

• Effective Renal Plasma Flow Study

  • Radiopharmaceutical: Tc99m MAG3
  • Dose: ???

• Glomerular Filtration Rate Study

  • Radiopharmaceutical: Tc99m DTPA
  • Dose: ???

• 2 Day MPI (Myocardial Perfusion Imaging)

  • Radiopharmaceuticals: Tc99m Tetrofosmin, Tc99m Sestamibi
  • Doses: 20-30 mCi

• 1 Day MPI

  • Radiopharmaceuticals: Tc99m Tetrofosmin, Tc99m Sestamibi
  • Doses: 10 mCi (Rest), 30 mCi (Stress)

• Dual Isotope MPI

  • Radiopharmaceuticals: Tl-201 Thallous Chloride, Tc99m Tetrofosmin, Tc99m Sestamibi
  • Doses: 3 mCi (Rest-Tl), 25 mCi (Stress-Tc)

• PET MPI

  • Radiopharmaceutical: Rubidium 82
  • Dose: 30-50 mCi (0.27-0.81 mCi/kg) (both rest/stress)

• Cardiac Viability Study

  • Radiopharmaceutical: F18 FDG
  • Dose: 10-15 mCi

• MUGA (Ventriculogram)

  • Radiopharmaceutical: Tc99m RBCs
  • Dose: 20-30 mCi

• Cardiac First Pass Study

  • Radiopharmaceutical: Tc99m DTPA
  • Dose: 20-30 mCi

• R-L Shunt Study

  • Radiopharmaceutical: Tc99m MAA
  • Dose: ???

• Myocardial Adrenergic/Cholinergic Intervention Study

  • Radiopharmaceutical: I-123 MIBG
  • Dose: 10 mCi

• Cardiac Amyloidosis Study

  • Radiopharmaceutical: Tc99m PYP
  • Dose: 10-20 mCi

• Infection Imaging

  • Radiopharmaceutical: Ga-67 Citrate
  • Dose: 5-10 mCi

• WBC Imaging

  • Radiopharmaceuticals: In-111 Oxine, Tc99m HMPAO
  • Doses: 500-600 uCi, 7-25 mCi respectively

• Breast Cancer Imaging

  • Radiopharmaceutical: Tc99m Sestamibi
  • Dose: 20-30 mCi

• Melanoma Lymphoscintigraphy

  • Radiopharmaceutical: Tc99m Filtered Sulfur Colloid
  • Dose: 100 uCi (4-8 injections)

• Breast Lymphoscintigraphy

  • Radiopharmaceutical: Tc99m Filtered Sulfur Colloid
  • Dose: 0.190-5 mCi split between 1-4 injections

• Lymphoscintigraphy

  • Radiopharmaceutical: Tc99m Tilmanocept
  • Dose: 0.5 mCi

• PET NET Imaging

  • Radiopharmaceuticals: Ga-68 DOTATATE, Ga-68 DOTATOC, Cu-64 DOTATATE
  • Doses: 0.054 mCi/kg up to 5.4 mCi, 4 mCi, 4 mCi respectively

• NET Therapy

  • Radiopharmaceutical: Lu-177 DOTATATE
  • Dose: 200 mCi every 8 weeks for 4 doses

• Liver Cancer Therapy

  • Radiopharmaceuticals: Y-90 TheraSphere (primary liver cancer), Y-90 SirSphere (mets from colorectal cancer)
  • Dose: 80-150 Gys, 2-3 GBq

• Pre-Therapy Y-90 Scan

  • Radiopharmaceutical: Tc99m MAA
  • Dose: 2-4 mCi

• Prostate Cancer Imaging

  • Radiopharmaceuticals: F18 Fluciclovine, F18 Piflufolastat, Ga-68 Gozetotide
  • Doses: 10 mCi, 9 mCi, 3-7 mCi respectively

• Prostate Cancer Therapy

  • Radiopharmaceutical: Lu-177 vipivotide tetraxetan
  • Dose: 200 mCi every 6 weeks for 6 doses

• PET Breast Cancer Imaging (ER+)

  • Radiopharmaceutical: F18 Fluoroestradiol
  • Dose: 6 mCi.

Adjunct Medications

• Brain SPECT

  • Pharmaceutical: Acetazolamide
  • Dose: 1 g in 10 mL sterile water.

• Cerebral Blood Flow Study

  • Pharmaceutical: Lidocaine
  • Dose: n/a.

• Cisternogram

  • Pharmaceutical: Lidocaine Cream
  • Dose: n/a.

• Cardiac MPI - Adenosine

  • Dose: 140 ug/kg/min for 6 min; radiopharmaceutical injected at 3 min (or infuse 4 min, inj at 2 min).

• Cardiac MPI - Regadenoson

  • Dose: 0.5 mg/5 mL IV rapid 10 sec injection followed by immediate saline flush; radiopharmaceutical injected 10-20 sec after.

• Cardiac MPI - Dipyridamole

  • Dose: 0.57 mg/kg IV over 4 min (or 142 ug/kg/min over 4 min); radiopharmaceutical injected at 3-5 min after.

• Cardiac MPI - Dobutamine

  • Initial Dose: Start with 5 ug/kg/min; increase by 5 ug/kg/min every 3 min up to 40 ug or until 85% of max HR achieved; continue stress infusion 2 min after radiopharmaceutical injection (done at peak stress).

• Cardiac MPI - Beta Blockers

  • Dose: 5 mg IV.

• Cardiac MPI - Atropine

  • Dose: 0.2-1 mg IV.

• Cardiac MPI - Aminophylline

  • Dose: 50-250 mg IV.

• Renal Scan (RAS) - Captopril

  • Dose: 25-50 mg orally 1 hour prior to study.

• Renal Scan (RAS) - Enalaprilat

  • Dose: 0.04 mg/kg in 10 mL saline over 5 min.

• Renal Scan (Diuretic) - Furosemide

  • Dose: 0.5 mg/kg up to 40 mg.

• HB Scan - Sincalide (CCK)

  • Dose: 0.02 ug/kg in 10 mL saline over 5 min.

• HB Scan - Morphine

  • Dose: 0.04 mg/kg in 10 mL saline over 2 min.

• HB Scan/Gastric Emptying

  • Ensure Drink: Boost Drink n/a.

• Meckel’s Diverticulum Study - Cimetidine, Rantidine, Famotidine

  • Dose: varies.

• Cardiac Viability - Insulin

  • Dose: 1-5 units (MD dependent).

• Thyroid Procedures - Recombinant TSH (rhTSH)

  • Dose: 0.9 mg MI for 2 days.

• WBC/RBC Scans - Acid-citrate-dextrose (ACD) solution

  • Dose: n/a.

• WBC/RBC Scans - Heparin

  • Dose: n/a.

• WBC Labeling - Hetastrach

  • Dose: n/a.

• Kit Preparation - Ascorbic Acid

  • Dose: n/a.

• MIBG/Pertechnetate Scans - Lugol’s Solution, Potassium Perchlorate

  • Dose: n/a.

Radiation Physics

Radionuclides

• Element

• Mode of Decay

• Half-life

• Principal Energy (keV)

  Element	Mode of Decay	Half-life	Principal Energy (keV)
  N-13	Positron	10 min	511
  F-18	Positron	110 min	511
  Co-57	EC	271 days	122
  Cu-64	Positron	12.7 hrs	511
  Ga-67	EC	78.2 hrs	93, 184, 300, 393
  Ga-68	Positron	68 min	511
  Ge-68	EC	270.8 days	n/a
  Rb-82	Positron	75 secs	511
  Sr-89	Beta	50.6 days	n/a
  Y-90	Beta	2.7 days	n/a
  Mo-99	Beta	66 hrs	740, 780
  Tc-99m	IT	6 hrs	140
  In-111	EC	2.8 days	171, 245
  I-123	EC	13.2 hrs	159
  I-125	EC	60 days	35
  I-131	Beta	8 days	364 (gamma)
  Xe-133	Beta	5.3 days	81
  Cs-137	Beta	30 years	662
  Sm-153	Beta	1.9 days	103
  Lu-177	Beta	6.6 days	498, 208, 113
  Tl-201	EC	73 hrs	167 (69-83 x-rays)
  Ra-223	Alpha	11.4 days	n/a

Nomenclature

• Isotope: Same atomic number and chemical properties.
• Isotones: Same number of neutrons, different number of protons.
• Isobars: Same mass number, different number of neutrons and protons.
• Isomers: Same number of neutrons and protons, different spins.
• Specific Activity: The radioactivity per unit mass of a radionuclide or a labeled compound.
• Carrier-Free: Containing no stable isotope detectable by ordinary analytical methods (also called no carrier added).
• Nuclear Force: Binding force within atomic nucleus that holds protons and neutrons.

Mass Defect

• Definition: Difference in mass between the mass of a nucleus (which is always less) and the combined masses of nucleons.

Transient Equilibrium

• Definition: Difference in TP (transformation products) by a factor of 10-50.

Secular Equilibrium

• Definition: Difference in TP by a factor of 100.

Radiation Safety

NRC Radiation Limits

Time for Monitoring Packages

• Timeframe: 3 hours following delivery during normal hours (within 3 hours of next workday if delivered outside normal hours).

Area for Package Wipe

• 300 cm²

Package Wipe Limit

• 6600 dpm

Decay in Storage Requirement

• TP: < 120 days

Bioassay Limits for I-131

• Open Bench: 1 mCi
• Fume Hood: 10 mCi
• Glovebox: 100 mCi

Timing for Bioassays

• Between 72 hours and 14 days

Written Directive Requirement

• Using 30 uCi or higher of I-131 or any other therapeutic agent

Acceptable Measured Dose Range

• ±20%

Release of Therapy Patient

• 500 mrem to other individuals
• Release of I-131 Patient: Administered less than 33 mCi OR GM reading of < 7 mrem/hr at 1 m
• Release of High Dose I-131 Patient: TEDE of 0.5 rem to other individuals

Written Instructions Given

• 100 mrem to other individuals
• Interrupting Breastfeeding: 100 mrem to nursing infant

Packaging Labels

White I Label (mR/hr)

• < 0.5 at surface, not detectable at 1 m

Yellow II Label (mR/hr)

• > 0.5 < or equal to 50 at surface
• < 1 at 1 m

Yellow III Label (mR/hr)

• > 50 < or equal to 200 at surface
• > 1 < or equal to 10 at 1 m

Breakthrough Limits

• Moly Breakthrough: 0.15 uCi Mo99/mCi Tc99m
• Aluminum Breakthrough: 10 µg Al/mL
• Sr-82 Breakthrough: 0.02 uCi Sr82/mCi Rb82
• Sr-85 Breakthrough: 0.2 uCi Sr85/mCi Rb82

Medical Event Requirements

• The dose exceeds 5 rem EDE or 50 rem to an organ or tissue or skin if any of the following occur:
  1. Total dosage delivered differs from prescribed dosage by 20% or more or falls outside the prescribed dosage range
  2. Administration of wrong radioactive drug
  3. Administration by wrong route
  4. Administration to wrong individual

Reporting to NRC

• Notification to NRC Operations Center by telephone within 1 calendar day of discovery
• Written report to NRC Regional Office within 15 days of discovery.
• Patient notification must occur within 24 hours after the discovery.
• Annotated report must include patient identifiers and must be submitted within 15 days of incident.

Radiation Biology

Stochastic vs Non-stochastic Effects

1. Stochastic Effects:

   • Random effects
   • Probability increases with increasing dose (no threshold)
   • Severity does not increase
   • Examples: cancers, regulations around ALARA (As Low As Reasonably Achievable)

2. Non-stochastic (Deterministic) Effects:

   • Effects resulting from high radiation doses
   • Severity increases with increasing dose
   • Threshold exists below which no damage is evident
   • Examples: cataracts (200 rads to eye), skin erythema

Radiopharmacy

Cell Labeling Procedures

• Leukocyte Labeling

  • Material: Tc99m HMPAO
  • Procedure:
  1. Collect 43 mL of whole blood in 7 mL of ACD, add 10 mL of 6% hetastarch, incubate for 45 min for sedimentation.
  2. Remove leukocyte rich plasma (LRP) and centrifuge at 450g to pellet white blood cells (create WBC button).
  3. Save LPP
  4. Mix WBC button with 30 mCi fresh Tc99m HMPAO and wait for 15-20 min.
  5. Centrifuge at 450g to remove unbound Tc99m
  6. Re-suspend labeled WBCs in patients' LPP for reinjection into the patient.
  7. Utilize within 1-3 hours after preparation.

• In-111 Oxine Procedure

  1. 43 mL blood diluted with 7 mL ACD or 400 units heparin plus 6 mL 6% hetastarch.
  2. Sediment for 50-60 min.
  3. Transfer plasma and centrifuge at 200g for 5 min.
  4. Suspend in 5 mL saline. Centrifuge at 200g, 5 min. Repeat centrifuge at 2000g for an additional 5 min.
  5. Suspend in 5 mL saline. Add 0.7-1.0 mCi (25.9-37 MBq) In-111 oxine
  6. Incubate for 30 minutes at room temperature.
  7. Add 10 mL of PPP (platelet poor plasma). Centrifuge at 250g for 8 min.
  8. Wash with 5 mL PPP and suspend in 5 mL PPP.
  9. Inject 500 uCi (18.5 MBq) In-111 labeled leukocytes.

• Red Blood Cell Labeling

  1. In vivo Method (60-90% labeling efficiency):
     • Administer stannous PYP IV 10 mg/kg weight, wait 15-30 minutes then inject 20 mCi pertechnetate.
  2. Modified In vivo Method (90-95% labeling efficiency):
     • Inject cold PYP IV, wait 15-30 minutes. Withdraw blood into heparin syringe with 20 mCi pertechnetate and mix. Incubate syringe for 10 minutes at room temperature and reinject whole blood.
  3. In vitro Method (≥ 98% labeling efficiency):
     • To vial with Sn2+ compound, add 3-5 mL anticoagulated blood. Incubate for 15 min. Then add 25 mCi Tc99m pertechnetate, add Na hypochlorite to destroy extracellular Sn2+ ion, and citrate buffer. Incubate for 20 min.

Tc99m Kit Preparation

• Pertechnetate:

  • Eluted from Mo-Tc generator in saline solution
  • Shelf Life: 12 hours at room temperature
  • Oxidation State: 7+

• Tc99m MAA (Macroaggregated Albumin)

  • Particle Size: 10-90 µm with none larger than 150 µm
  • Stored at: 2-8°C before labeling
  • Labeling Procedure:
    1. Warm the kit to room temperature.
    2. Add pertechnetate.
    3. Shelf Life: 6-8 hours, stored at 2-8°C.

• Tc99m MDP (Methylene Diphosphonate)

  • Labeling: Add pertechnetate to the kit and mix.
  • Shelf Life: 6 hours, stored at 15-30°C.

• Tc99m SC (Sulfur Colloid)

  • Labeling Procedure:
    1. Add acid to the mixture of pertechnetate and sodium thiosulfate.
    2. Heat to 95-100°C in water bath for 5-10 min.
  • Shelf Life: 6-12 hours at room temperature
  • Oxidation State: 7+
  • Particle Size: < 1 µm (mean size of 0.3 µm); <1 µm for lymphoscintigraphy.

• Tc99m Tilmanocept

  • Labeling Procedure:
    1. Add pertechnetate to the reaction vial and let stand for 15 minutes.
  • Shelf Life: 6 hours at room temperature.

• Tc99m DTPA (Pentetate)

  • Labeling Procedure: Add pertechnetate to the kit and mix.
  • Shelf Life: 6 hours, stored at 15-30°C.

• Tc99m Mebrofenin

  • Labeling Procedure: Add pertechnetate to the kit and mix.
  • Shelf Life: 18 hours, stored at 15-30°C.

• Tc99m HMPAO (Exametazime)

  • Labeling Procedure:
    1. Add pertechnetate to the kit (must not be older than 2 hours since elution and from a generator that has been eluted in the past 24 hours).
  • Shelf Life: 30 minutes (if methylene blue is added: 4 hours).

• Tc99m Sestamibi

  • Labeling Procedure:
    1. Add pertechnetate to the kit.
    2. Heat mixture in boiling water for 10 minutes.
  • Shelf Life: 6 hours, stored at 15-30°C.

• Tc99m MAG3 (Mertiatide)

  • Labeling Procedure:
    1. Add pertechnetate to kit vial.
    2. Introduce filtered air.
    3. Heat at 100°C in water bath for 10 minutes.
    4. Cool for 15 minutes.
  • Shelf Life: 6 hours, stored at 15-30°C in the dark.

• Tc99m ECD (Bicisate)

  • Labeling Procedure:
    1. Add pertechnetate to vial B.
    2. Add aliquot from vial A.
    3. Wait 30 minutes at room temperature.
  • Shelf Life: 6 hours, stored at 15-30°C.

• Tc99m Tetrofosmin

  • Labeling Procedure:
    1. Add pertechnetate to kit vial.
    2. Incubate for 15 minutes at room temperature.
  • Shelf Life: 8 hours, stored at room temperature.

• Tc99m DMSA (Succimer)

  • Labeling Procedure:
    1. Add pertechnetate to kit vial.
    2. Incubate for 10 minutes at room temperature.
  • Shelf Life: 6 hours, stored at 15-30°C in the dark.