In Vivo Evaluation Using Gamma Scintigraphy

The authors discuss gamma scintigraphy as a technique for in vivo evaluation of drugs and delivery systems.
Nov 02, 2010
Volume 34, Issue 11

To enhance patient compliance and treatment efficiency, several investigators have focused on developing novel routes of drug delivery or reducing the multiple dosing regimens to once-daily products in the form of controlled-release formulations (1). In vitro release studies using conventional and modified dissolution methods can provide insight into the performance of drug-delivery systems, and radionuclides incorporated into the dosage form provide information on the in vivo behavior of dosage forms. Gamma scintigraphy is a well-established radionuclide imaging technique (2). This technique is valuable for evaluating various dosage forms. It is noninvasive and provides reliable information on the transit time of dosage forms in different regions of the gastrointestinal (GI) tract and various other body organs. Gamma scintigraphy can analyze the time taken for disintegration of the drug product and the site where disintegration occurs. The effect of different conditions such as the presence of food, diseased state, and dosage size also can be explored. In current experimental protocols, it is common to evaluate the in vivo performance of drug-delivery systems in healthy volunteers or patients using this imaging technique (3). The process is significantly different from traditional techniques such as diagnostic X-ray methods where external radiation is passed through the body to form an image (4). Contrary to this approach, the gamma scintigraphic technique relies on the detection of radiation emitted from radionuclides tagged with dosage forms that are administered intravenously or orally. Release of the tagged tracer is monitored rigorously in vitro. Moreover, this technique should be performed in a protected environment (1).

Gamma scintigraphy

In gamma scintigraphy, nuclear imaging is generally carried out with planar or single photon emission computed tomography (SPECT) cameras capable of detecting the incorporated radionuclides that emit gamma radiation with energies between 100 and 250 KeV (5). Emitted radiations are further captured by external detectors such as gamma cameras. The following are advantages of gamma scintigraphy:

  • Very little radiation exposure to the participating subjects compared with roentgenography (i.e., X-ray methods)
  • Qualitative, as well as quantitative, observations that can be recorded that are not feasible with other techniques
  • Totally noninvasive
  • In vivo evaluation of dosage forms is possible under normal physiological conditions.

Radiolabeling of dosage forms

Table I: Properties of commonly used radionuclides.
Before imaging by this technique, the dosage form should be radiolabeled. Radiopharmaceuticals labeled with 99mTc are most commonly used; however, other sources of radionuclides that can be used in traditional gamma scintigraphy are 81mKr, 111In, 123I, and 131I (6, 7). Table I represents half-life and the types of emitted radiation of these radionuclides. A suitable radionuclide for scintigraphic studies is selected by considering the following factors (8):
  • Radiation energy of gamma rays should be within the detection range of the gamma camera
  • Emitted radiation well-suited for in vivo applications
  • The half-life of the radionuclide must be adapted to the period of testing
  • The tracer should not alter the performance of dosage forms being investigated
  • Cost and availability.

The radionuclide is incorporated into the formulation using an appropriate radiolabeling technique, so it can act as a marker for a particular event. Usually, dosage forms are assessed to determine the release of a drug, but in some cases, the radionuclide is required to be retained in the formulation to investigate the ultimate fate of the dosage form in terms of site, rate, and extent of drug absorption. The observed transit of the dosage form also can be correlated with the rate and extent of drug absorption (9).

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