Nanoparticles for Bioimaging: Analytical Characterization and Measurements - Nanotechnology for Biomedical Imaging and Diagnostics - page 160

6.5 radioactivity measuremeNt of NaNoparticles

Radioactivity measurement involves detection of “radioactive decay” of the radionuclide.
Common radioactive decay process involves alpha (α, 4 He) decay, beta (β, e − ) decay,
positron (β + ) decay, or gamma (γ, photon) decay. The radioactive decay can be
detected by a variety of radiation detectors such as survey meters, dose calibrators
(gas-filled detectors), inorganic and liquid scintillation detectors, and semiconductor
(ge, Si) detectors. Nuclear medicine imaging modalities such as planar imaging,
single-photon emission computed tomography (SPECT) imaging, and positron
emission tomography (PET) imaging involve the use of radioactive decay property of
radionuclides for detection and therapy of disease. a gamma camera obtains an
image of the distribution of a radiopharmaceutical in the body (or organ) by detection
of emitted γ-rays. gamma cameras are used for planar and SPECT imaging. Common
gamma-emitting radionuclides are ga-67 ( t 1/2 = 78.26 h), Tc-99m ( t 1/2 = 6.02 h), In-111
(2.83 d), I-123 (13.2 h), I-131 (8.04 d), and Tl-201 (3.04 d). PET relies on the detec-
tion of coincident 511 keV photon pairs generated when a positron annihilates with
an electron in tissue. Positron-emitting radionuclides commonly used clinically and
preclinically are C-11 ( t 1/2 = 20.38 m), N-13 ( t 1/2 = 9.965 m), o-15 ( t 1/2 = 122.24 s),
f-18 ( t 1/2 = 109.77 m), Cu-64 ( t 1/2 = 12.7 h), ga-68 ( t 1/2 = 68 m), Zr-89 (78.5 h), Br-76
(16.2 h), and Rb-82 ( t 1/2 = 1.3 m). Both PET and SPECT are considered highly
sensitive, quantitative, and translational to clinic.
Radioactivity measurement of nanoparticles is a critical step before using the
radiolabeled nanoparticle for in vitro or in vivo applications. The radioactivity
measurement quantifies the radiolabeling efficiency (percent labeling yield), distin-
guishes the “free” radioactive label from the conjugated radioactive label, and deter-
mines the specific activity (amount of radioactivity per unit of mass of a radionuclide
or labeled compound) of the radiolabeled nanoparticle. Common units of specific
activity are Ci/mmol or Bq/mmol, and specific activity is inversely proportional to
the half-life ( t 1/2 ) of the radionuclide. accurate measurement of radioactivity is con-
sidered key to developing effective radiolabeling conditions. In principle, higher
specific activity is desirable as high specific activity translates to high-detection
sensitivity toward targeted proteins in vivo under the confines of “tracer” principle.
However, one of the challenges with labeling nanoparticles or small molecules with
radionuclides is the presence of significant amounts of cold (“nonradiometal”) impu-
rities that interfere with effective radiolabeling at high specific activities.
The high specific activity of the radionuclide would translate into high specific
activity of the radioconjugated nanoparticle. a common method used to determine the
effective specific activity (ESa) for the commonly used PET radionuclide Cu-64 is by
radiolabeling titrations with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
(DoTa) and/or 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETa).
Briefly, the titration involves mixing macroscopic quantities of copper, using 64 Cu as
a tracer, with DoTa or TETa on an equimolar basis. The minimum DoTa/TETa
concentration where 100% labeling occurs is assumed to be equal to the concentration
of Cu(II) present [1]. Recently, an elegant lC-MS approach was proposed to quantify
nonradioactive transition metal impurities in metal radionuclides [2].