renal imaging agents parts 1 and 2

kidney functions related to NM imaging

excretion of metabolic wastes

three kidney regions

cortex (outer layer), medulla (renal pyramids), pelvis (central cavity)

nephron

functional unit of the kidney

primary mechanisms of action for nephrons

glomerular filtration, tubular reabsorption, tubular secretion

one kidney has about how many nephrons?

1 million nephrons

components of a nephron

glomerulus, proximal convulated tubule, loop of henle, distal convulated tubule, collecting duct

nephron blood supply

renal artery, afferent arteriole, efferent arteriole, peritubular capillary network

blood pressure is ___ in glomerulus because…

higher; efferent arteriole is smaller than afferent

excretion formula

F-R+S

substances are removed from blood by

glomerular filtration and tubular secretion

reabsorption

occurs in tubule, where essential substances in the glomerular filtrate are reabsorbed into blood

substances ned to be ___ to have a small molecular size

non-protein-bound

small molecules in the glomerulus are

glomerular filtrate

larger molecules in glomerulus…

stay in the blood vessel (e.g. proteins and blood cells)

how are filtrates moved out of glomerulus

passive diffusion

nutrient and salt molecules are actively reabsorbed how?

FROM convoluted tubules INTO peritubular capillary network (blood)

water flows passively

tubular secretion- certain ions and molecules are actively secreted…

FROM peritubular capillary network (blood) INTO the convuoluted tubules

plasma clearance

volume of plasma from which a drug is completely removed by the body per unit of time

plasma clearance only provides info about…

amount of drug removed from blood that appears in urine; not applicable to drugs stored, synthesized, metabolized by the kidney

plasma (renal) clearance formula

= (urine concentration of drug x urine volume) / plasma concentration of drug

if a freely filterable drug (minimal plasma protein binding) has a clearance less than the GFR…

then it must undergo some degree of tubular reabsorption

if a substance has a clearance of greater than the GFR…

it must undergo tubular secretion

normal GFR

125 mL/min

extraction efficiency (ratio)

measure of amount of drug eliminated into urine and retained by kidney

defined as fraction of a substance removed from plasma during one circulation through kidney

extraction ratio formula

= (renal arterial concentration of drug - renal venous concentration of drug) / renal arterial conc of drug

if all drug is removed from blood in a single pass through the kidney…

extraction ratio will be 1.0

if no drug appears in urine, then

it’s completely retained by kidney, would be good renal imaging agent bc drug is bound in the kidney

if all drug appears in the urine and none retained in kidney…

it would be a good agent for measuring renal plasma flow and tubular function

if none of drug is removed from blood in a single pass through the kidney…

ER will be 0.0

if drug is not bound, secreted, or absorbed, then…

it’s a good candidate for assessing GFR

radiopharmaceuticals for renal imaging

tc99m succimer (DMSA)

tc99m gluceptate

radiopharmaceuticals for renal clearance (tubular secretion)

rc99m mertiatide (MAG3)

i-131-o-iodohippurate (OIH)

radiopharmaceuticals for renal clearance (GFR)

tc99m pentetate (DTPA)

i-125 iothalamate

significance of renal imaging drugs

all bound in kidney (good renal anatomic agent)

significance of tubular secretion drug

none bound in kidney- good renal tubular agent

clearance is 650 mL/min

significance of glomerular filtration agents

none bound, secreted, or reabsorbed; only filtered (good GFR agents)

clearance is 125 mL/min

renal NM drugs only localize via…

filtration, secretion, or both

for a drug to be secreted, it must undergo…

facilitated diffusion or active transport (organic ion, reversible protein-bound)

which radiopharmaceuticals localize through binding?

succimer, glucoheptonate (tc99m both)

which radiopharmaceuticals localize through secretion?

tc99m mertiatice and i-131 hippuran

which radiopharmaceuticals localize through filtration?

tc99m pentetate and i-125 iothalamate

hippuran (i-131 OIH)

first widely used rp for assessing renal function; tubular secretion is how it’s eliminated; was choice of renal function for 30+ years

replaced by mag3

OIH has poor ___, a ___ radiation dose per imageable photon

poor imaging properties, high rad dose

cannot be used to image renal perfusion

DTPA

filtered, not secreted!

became agent of choice in 60’s for GFR studies

couldn’t be used for tubular secretion!

both DMSA and GH bind to renal cortex, making them good choices for…

imaging the renal parenchyma

DMSA is approximately ___ bound in renal tubules

40%

gluceptate is only ___ bound in renal tubules

~12%

while DMSA reaches high conc in cortex, it is…

slowly cleared, bc of high plasma protein binding, making it a poor choice for eval the renal collecting system

radionuclide cortical scintigraphy w tc99m DMSA or glucoheptonate is ideally suited for…

renal morphology eval, since these agents are conc in renal cortex by binding to cells of PCTs

PCTs located where

within the cortex

DMSA succimer features

highly protein bound

low urinary excretion

high cortical binding

distributed in plasma

activity cleared slowly by secretion

very small amt cleared within 2 hours

glucoheptonate (GH)

it’s a carb

moderate amt of urinary excretion

moderate amt of cortical binding

activity rapidly cleared from plasma, filtered drug eliminated through collecting duct system

almost half the activity is excreted in urine within an hour

DMSA prod ___ images of renal cortex…

high res images without interference from urinary activity

early GH images permit assessment of…

renal perfusion and eval of renal collecting systems/ureter (looks similar to DTPA at this stage)

early images also demonstrate renal cortex, remains well visualized several hours after admin

Tc99m DSMA is preferred cortical imaging agent why?

its binding is much higher than Tc99m GH, minimal urinary collecting system interference

normal DMSA uptake

homogenous, bilateral uptake in cortices

abnormal DMSA uptake

hypoactive areas- renal parenchymal scarring, pyelonephritis

DMSA target organ, critical organ

kidney cortex for both

glucoheptonate (GH) target/critical organ

target- kidneys

critical- bladder

DTPA pentetate

distributed in plasma- does not bind to much but some proteins

rapid clearance, not secreted/reabsorbed

distribution in renal vasc space then urine thereafter

iothalamate (glofil)

same as DTPA, except NO BINDING!!!

renal clearance for DTPA

approx 20% of renal plasma flow (i.e. 125 mL/min)

cleared by glom. filt. with NO tubular reabsorption/secretion

DTPA does have some ___

binding; this GFR method must include a correction for plasma protein binding

iothalamate (glofil) renal clearance closely approximates

inulin (lab testing and gold standard for GFR)

NO tubular reabsorption/secretion

MUST BE TAGGED TO RAI because I-125 photons are almost entirely attenuated by tissue

99mTc DTPA is preferred GFR agent because

it uses tc99m; has variable % to which it’s protein bound, makes it less reliable than measuring inulin

pentetate (DTPA) target/critical organs

(P) target- kidneys, critical- bladder

iothalamate (glofil) target/critical organs

(I) target- kidneys, critical- bladder

explain the green, yellow, blue, pink lines

green- equilibrium of DTPA bolus w extracellular fluids

yellow- plasma protein binding (4-10%)

blue- slope using pt measurements; X’s = blood samples (measurements)

pink- true GFR

in GFR assessment, a linear regression is done to do what?

get a concentration at time 0; that number is used in an equation with the 4 sample counts to calc GFR

renal blood flow

RBF- total blood + plasma (w components)

renal plasma flow

RPF- plasma (w components)

renal plasma flow is sometimes described as

tubular extraction rate

renal tubular secretion is an assessment of

renal plasma flow

secretion drugs are removed from the blood via

active tubular secretion by organic anion transporter located on membrane of PCT renal tubules

mertiatide (MAG3)

distributed in blood’s plasma, significantly binds to plasma proteins

activity rapidly cleared via secretion

rapidly secreted in urine within 30 min

peak conc in kidneys at 3-5 min

iodohippurate (hippuran)

large % binds to plasma proteins

activity rapidly clear; some filtration of drug that wasn’t protein bound

rapidly secreted, 30 min most of it

peak conc in kidneys is 3-5 min

MAG3 renal extraction and clearance is…

high! tagged to Tc99m; preferred for renal flow imaging because of this, demonstrates detailed anatomic info

hippuran must be

tagged to RAI; i-131 photons not able to be imaged w as much detail as tc99m

MAG 3 AND iodohippurate target/critical organs

target is kidney, critical is bladder

dosage for 99mTc DTPA, GH, MAG3 radiopharmaceuticals

10 mCi

dose for 99mTc DSMA

5 mCi

131 I-OIH dose

100 uCi/kidney