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characteristics of ideal RP
- availability
- short T 1/2
- no particle emission
- metabolic suitability
- high target / non target ratio
- preferred mode of decay
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mechanisms of localization
Phagocytosis, capillary blockade, active transport, simple diffusion, cell sequestration, compartmental localization, antigen antibody complex.
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Phagocytosis;
- removal of forgein matter by physical entrapment.
- Tc-99 S.C. RES
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Capillary blockade;
- mechanical obstruction of capillaries or precapillaries arterioles in lung,
- MAA
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Active Transport;
- Cellular metabolism concentrates RP in organ or tissue.
- 123-I NaI for thyroid function/imaging
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Simple diffusion;
- movement of RP from area of higher concentration to area of lower concentraion.
- breakdown of BBB allows RP to penetrate brain in area of affected tissue.
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Cell sequestration;
- Removal of old or damaged RBCs from circulation by spleen; uptake of WBCs in infection sites.
- 51-Cr RBCs taken up by spleen
- 111-In WBCs sites of infection.
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Compartmental localization;
- introduction of RP into well-defined body compartment where it remains for and extended period.
- -99m Tc DTPA aerosol, 133Xe technegas
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Antigen-Antibody complex formation;
- radiolabeled antibody binds to tumor associated antigen.
- using tumor specific labeled antibodies to detect cancer of stage therapy.
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Mechanisms affecting biodistribution;
- Blood flow
- Particle size
- Protien binding
- iatrogenic alterations
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Blood Flow;
For most of NM the circulatory system transports the RP via venous blood supply.
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Particle size;
Removed from circulation ether by RES or lungs depending on size.
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Protien binding;
most RPs bind to plasma protiens ( Albumin in many cases) plasma clearance affected if bound tightly.
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Iatrogenic alteration;
- causing a secondary condition arising from treatment of a primary condition.
- -undesirable-> thyroid: iodine contrast media affecting uptake. BoNE: poor uptake due to iron overload.
- -Desirable-> Renal imaging: admin of furosmide to rule out mechanical obstruction, MPI admin of persantine to dialate heart vessels.
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Clinical investigation of new drugs.. steps
- Preclincal studies
- eIND ( exploratory investigational new drug)
- IND (investigational new drug) phase 1 -3
- NDA (new drug application)
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Preclinical Studies;
performed on animals to determine biodistribution, kinetics , toxicity, dose estimitates , lethal , sublethal
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eIND
- limited human exposure
- no therapeutic of diagnostic intent
- limitied duration of dose.
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Phase 1 clinical study
- 20-80 people
- pharmacology studies in normal volunteers to find normal biodistributions in humans.
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Phase 2 clinical study
- 100-300 people
- studies of patients with specific disease/condition
- determine additional evidence of safety and inital evidence of diagnostic or therapeutic efficacy.
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Phase 3 clinical study;
- 1000-3000 people
- determine optimum dose
- establish addional uses
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NDA
all commercially distributed RPs must be approved through the FDA and be assigned an NDA number.
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Phase 4 clinical study
Post Market Surveillance
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Adverse reactions
- cardio pulmonary decompression
- -heart failure, type A : expected , dose dependant. Type B; unexpected, hypersensitivity.
- idiosyncratic reaction; unusual individual response
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target organ
organ being imaged
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critical organ
organ or body part receiving most of radiatin dose.
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source organ
organ or body part delivering radiaiton dose to target organ (can be target organ delivering dose to self)
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rad
- absorbed dose.
- quantity of radiation enegry deposited in an absorber per gram of absorber
- 1 rad = 100 ergs/gram
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g.rad
- integral dose
- the total amount of energy deposited in a volume of tissue.
- g.rad = absorbed dose x tissue mass (grams)
- 1 g.rad = 100ergs of energy deposited in a vol of tissue
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Absorbed fraction
the fraction of energy of radiation emitted from a source organ that is absorbed in a target organ.
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DOT 1 (white)
- contact .05mR/hr
- at 3ft NDR
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DOT II (yellow)
- contact 50mR/hr
- 3ft 1mR/hr
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DOT III (yellow)
- contact 200mR/hr
- 3ft 10mR/hr
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The transport index should have the...
name of isotopes being delivered and the amount of exposure reading at 1 meter
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Ionic agents;
- divide into charged particles when in a solution.
- high osmolar contrast 1300-1600 mOsm/kg
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Non-ionic agents
- do not divide into particles when in a solution.
- no degradation in the blood stream.
- low osmolar contrast 500 to 850 mOsm/kg
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osmolality
the concentration of molecular particles in the contrast agent solution.
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All IV contrast has a osmolality.....
- greeater than blood plasma. 285 mOsm/kg
- so IV contrast is Hypertonic compared to blood plasma. causing movement of water from tissues into vascular space. dyhadrating the patient.
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