Dr Taj Khan Dept. of Pharmaceutical Chemistry, OCP, Sanpada.

Radiopharmaceuticals (nuclear medicine)

P’cal formulations consisting of radioactive substances (radioisotopes and molecules labelled with radioisotopes), used either in diagnosis or therapy or imaging

Radiation refers to particles or waves coming from the nucleus of the atom (radioisotope or radionuclide) through which the atom attempts to attain a more stable configuration.

Isotopes of an element are nuclides with the same atomic number ‘Z’ but different mass numbers ‘A’ Radionuclide: Nuclides containing an unstable arrangement of protons

Radioactivity: The phenomenon of emission of radiation owing to the spontaneous transformation or disintegration of the radionuclide and neutrons

Units of Radioactivity: In the International System (SI), the unit of radioactivity is one nuclear transmutation per second and is expressed in Becquerel (Bq), named after the scientist Henri Bequerel.

The old unit of radioactivity was Curie (Ci), named after the scientists Madame Marie Curie and Pierre Curie, the pioneers who studied the phenomenon of radioactivity. One Ci is the number of disintegrations emanating from 1 g of Ra226, and is equal to 3.7 x 1010 Bq.

Difft no of neutron

• Half-Life Period: The time in which a given quantity of a radionuclide decays to half its initial value (T1/2).

• Radionuclide generator: Any system or device incorporating a fixed parent radionuclide from which is produced a daughter radionuclide is extracted by elution or by any other method. e.g., the most widely used radionuclide generator in radiopharmacy is 99Mo-99mTc generator.

A very heavy radionuclide may attain stability by shedding some nucleons. Such transformations may involve emission of charged particles, The charged particles emitted from the nucleus may be 3 types AlfaBetaGamaa

α particles (He nucleus of mass number 4) Radioactive nuclei having too many nucleons (n and p) often undergo α decay, in order to achieve nuclear stability. α particle has a mass of 4 units and a charge of +2 units, and is therefore, equivalent to helium +2 ion. α particles are relatively slow and heavy and have a low penetrating power. Have a large charge, so α particles ionize other atoms strongly.

Beta (β) particles: Negatrons

-vely charged

Nuclei having neutrons in excess than what is needed for a stable configuration mostly undergo β- decay, in order to achieve nuclear stability.

β particles have a charge of -1. (Same as e)

Atomic mass is unchanged the atomic number or by 1.

They are fast, and light. medium penetrating power.

Can ionize atoms but wkr than α

Gamma (γ) rays:

Energetic photons of electromagnetic radiation and no charge or mass. electromagnetic rays coming out of nucleus as a result of the difference in nuclear energy levels of the excited and the ground states of the daughter nuclide when a nuclear transmutation takes place.

Energy greater than those of X-rays.

waves, not particles.

Gamma rays have a high penetrating power

Gamma rays do not directly ionize other atoms, although they may cause atoms to emit other particles which will then cause ionization.

Penetrating power: Alpha particles may be completely stopped by a sheet of paper, beta particles by aluminum shielding. Gamma rays can only be reduced by much more substantial mass, such as a very thick layer of lead.

Radioactive decay At an exponential rate with a particular decay constant which is a characteristic of each radionuclide. The exponential decay (decay curve) is described by the equation: At = Ao e-λt

At = the radioactivity at time t, Ao = the radioactivity at time t = 0, λ = the decay constant characteristic of each radionuclide, e = the base of Napierian logarithms. The half-life (T1/2) is related to the decay constant (λ) by the equation:

T1/2 = 0.693/ λ

The radionuclide is generally identified by its half-life or by the nature and energy of radiation or radiations emitted as prescribed in the monograph.The T1/2 is measured with a suitable detection apparatus detector such as ionisation chamber, Geiger-Müller counter, scintillation counter (solid crystal or liquid) or a semiconductor detector.

1) Treatment of disease: They are radiolabeled molecules designed to deliver

therapeutic doses of ionizing radiation to specific diseased sites. e.g. cancer

2) As an aid in the diagnosis of disease: The radiopharmaceutical accumulated in an organ of interest

emit gamma radiation which are used for imaging of the organs with the help of an external imaging device called gamma camera

Chromium 51 (51Cr)

Radioactive isotope of chromium having a T1/2 27.7 & decaying by electron capture, emitting gamma rays. It is used to label RBCs for measurement of red cell mass or volume, survival time, &sequestration studies, and for the diagnosis of GIT bleeding, & is used to label platelets to study their survival. RBC tagging agent for the determination of red cell survivalTo quantify gastro- intestinal protein loss.  

Iodine - 125• Chemical Symbol: 125I• Half-life:   59.4 days• Diagnostic use: Indicated for use in the determination of: • Total blood • Plasma volume evaluation of glomerular filtration • Total blood and plasma volumes • Cardiac output • Cardiac and pulmonary blood volumes and circulation times • Protein turnover studies • Heart and great vessel delineation • Localization of the placenta • Localization of cerebral neoplasm

I

131

53Xe

131

54

+ 0.608 Mev Beta + 3.64 Mev Gamma

• Performance of the radioactive iodide (RAI) uptake test to evaluate thyroid function

• Localizing thyroid malignancies Therapeutic: • Treatment of hyperthyroidism • Treatment of carcinoma of the thyroid

CO-60 and C0-57

Cobalt-60 (10.5 mth): used for external beam radiotherapy.Cobalt-57 (272 d): Used as a marker to estimate organ size and for in-vitro diagnostic kits.

CO

57

27Fe

57

26

+ 1.23 Mev Gamma

Proton bumbardment

CO

60

27Ni

60

26

+ 0.312 Mev Beta + 1.17 Mev Gamma + 1.33 Mev Gamma

CO-60

Abs & meta of Vit B12 1 Micro curie oral or im routeGFR of kidney functioningMatallic wire/ seeds implanted into body cavities – Treatment of advance cancer of cervix, mouth vagina, uterus & bladder

Iron-59

Iron-59 (46 d): Irradiation of Fe 58 Beta & Gamma

Used in studies of iron metabolism in the spleen.Ferric citrate Fe-59 inection –diagnosis of haematological disorders related to Fe metabolism & RBC formation dose 5-50 micro curie

Fe

59

26CO

59

27

+ 0.462 Mev Beta + 0.271 Mev Beta + 1.30 Mev Gamma + 1.1 Mev Gamma

Gold 198

Gold-198 is currently one of the limited treatments for cancer. This isotope can cure prostate, cervix, and bladder cancer. Rheumatoid arthritis. "disodium aurothiomalate" which is an injection used to treat the disease. The isotope has also other medical uses as imaging and scanning body parts for diagnostic use. SE: radiation sickness.

Technetium-99m• Diagnostic use: • Diagnosis of acute cholecystitis • As a hepatobiliary imaging agent• As an adjunct in the detection of altered regional cerebral perfusion

in stroke.• Leukocyte labeled scintigraphy as an adjunct in the localization of

intra abdominal infection and inflammatory bowel disease.An adjunct in the evaluation of pulmonary perfusion (adult and

pediatric)

Technetium-99m• As a bone imaging agent to delineate areas of altered osteogenesis.• In patients > 30 days of age as a renal imaging agent for use in the

diagnosis of:• Congenital and acquired abnormalities• Renal failure• Urinary tract obstruction and calculi• Diagnostic aid in providing:• Renal function• Renal angiograms• Renogram curves for whole kidney and renal cortex• As a bone imaging agent to delineate areas of altered osteogenesis

(adult and pediatric use)

Technetium-99m• • Brain imaging • Kidney imaging: - To assess renal perfusion - To estimate glomerular filtration rate• As a bone imaging agent to delineate areas of altered osteogenesis• As a cardiac imaging agent used as an adjunct in the diagnosis of

acute myocardial infarction• As a blood pool imaging agent useful for:- Gated blood pool imaging- Detection of sites of gastrointestinal bleeding

Technetium-99m®

•Diagnostic use: Myocardial perfusion agent that is indicated for:•Detecting coronary artery disease by localizing myocardial ischemia (reversible defects) and infarction (non-reversible defects)•Evaluating myocardial function•Developing information for use in patient management decisions•Planar breast imaging as a second line diagnostic drug after mammography to assist in the evaluation of breast lesions in patients with an abnormal mammogram or a palpable breast mass

Technetium-99m• Diagnostic use: • Brain Imaging (including cerebral radionuclide

angiography)* • Thyroid Imaging* • Salivary Gland Imaging • Placenta Localization • Blood Pool Imaging (including radionuclide angiography)* • Urinary Bladder Imaging (direct isotopic cystography) for the

detection of vesico-ureteral reflux* • Nasolacrimal Drainage System Imaging (*adult and pediatric use)

Technetium-99m• Diagnostic use: Indicated for lymphatic mapping with a hand-held

gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma.

• Myocardial perfusion agent that is indicated for:• Detecting coronary artery disease by localizing myocardial ischemia

(reversible defects) and infarction (non-reversible defects)• The assessment of left ventricular function (left ventricular ejection

fraction and wall motion)• Imaging areas of functioning retriculoendothelial cells in the liver,

spleen and bone marrow* • It is used orally for: - Esophageal transit studies* - Gastroesophageal reflux scintigraphy* - Detection of pulmonary aspiration of gastric contents*

The effect of radioactive radiations on biological tissue depends on:

1) Penetration ability2)Energy of radiation3)Nature of tissue4) Surface area exposed

Destructive ability is directly related to its interaction with molecules present in the tissue to form abnormal amt of ions & or free radicals. these chem species can alter the local pH or serve to initiate free radical chain rxns, this results in production of peroxide & other toxic compounds. This leads to hostile environment for tissue which leads to necrosis & then tissue /organ destruction Since H2O is most abundant in body radiation reacts with it give free radical of H and OH which produce H2 and H2O2

• Radiation can cause immediate effects (radiation sickness), but also long term effects which may occur many years (cancer) or several generations later (genetic effects).

• Biological effects of radiation result from both direct and indirect action of radiation

• Direct action is based on direct interaction between radiation particles and complex body cell molecules, (for example direct break-up of DNA molecules)

• Indirect action is more complex and depends heavily on the energy loss effects of radiation in the body tissue and the subsequent chemistry.

• Resulting biological damage depends on the kind of alteration andcan cause cancer or long-term genetic alterations.

• OH radical attacks DNA-molecule.