Localization Mechanisms of Radiopharmaceuticals

Scintigraphic techniques have opened a new era of developments in the localization of infectious and cancerous foci. Diseases area targeting mechanisms of radiopharmaceuticals encompasses visualization, characterization, and measurement of physiological and biological functioning at targeted sites in addition to measure the area and density of the disease. The accumulation of a radiopharmaceutical at specific organ is based upon numerous processes such as enzymatic interactions, receptor binding site, transport of chemical species and elimination of damaged cells from circulation by a normal metabolic process. PET and SPECT are developing scanning techniques that provides effective diagnostic tool to identify pathophysiology of diseased cells. In this chapter, we are exploring and explaining different mechanisms of radiopharmaceutical localization for imaging and therapeutic processes. The knowledge of these mechanisms will help to develop target based new radiopharmaceuticals using variety of medically used radioisotopes either for imaging or therapy of diseased cells.

Single-Photon Emission Computed Tomography (SPECT) Radiopharmaceuticals

Nuclear medicine techniques have a great deal of advantage of using gamma radiation emitter radiolabeled compounds to diagnose the long list of infectious and malignant disorders in human systems. The gamma emitter radionuclide-labeled compounds are associated with single photon emission computed tomography (SPECT) camera. SPECT camera mainly offers the detection and analysis of gamma rays origin to furnish the imaging of defective organs in the body. There are about 85% radiopharmaceuticals in clinical practice which are being detected by SPECT camera. The following chapter is an update about the SPECT radiopharmaceuticals that were developed and tried for infection and cancer diagnosis.

Radiolabelled Nanoparticles for Brain Targeting

Tumors like glioblastoma are inaccessible due to blood brain barrier. The permeability of radioisotopes can be improved by conjugating them with nanoparticles. The most common malignant adult brain tumor is glioblastoma, which has very poor patient prognosis. The mean survival for highly proliferative glioblastoma is only 10–14 months despite an aggressive radiotherapy and chemotherapy following debulking surgery. β− particle emitters like 131I, 90Y, 186/188Re, and 177Lu have been coupled with nanoparticles and used for treatment of glioblastoma. These radiopharmaceutical compounds have resulted in a stabilization and improvement of the neurological status with minimal side effects. Similarly, α particle emitters like 213Bi, 211At, and 225Ac are an innovative and interesting alternative. Alpha particles deliver a high proportion of their energy inside the targeted cells within a few micrometers from the emission point versus several millimeters for β− particles. Thus, α particles are highly efficient in killing tumor cells with minimal irradiation of healthy tissues and permits targeting of isolated tumor cells. This has been confirmed by subsequent clinical trials which showed better therapeutic efficacy and minimal side effects, thus opening a new and promising era for glioblastoma medical care using α therapy.

Theranostics: New Era in Nuclear Medicine and Radiopharmaceuticals

Malignancy and many inflammatory diseases have become a major concern for mankind over the years. The conventional therapy of these diseases lacks the effectiveness of the better diagnosis and targeted treatment of these diseases, but nuclear medicine can be regarded as a savior in the current scenario. Over the years, radioactivity of radioisotopes has been employed for treatment of many diseases. Nuclear medicines came up with radiopharmaceuticals that impart the ability to destroy specific diseased cells with high-energy-emitting radionuclides. Moreover, the emergence of theranostics, which is a combination of single drug used both for diagnostic as well as therapeutic purpose, has added a new feather in the field of nuclear medicines for providing a specific and personalized treatment to the patient. The current chapter discusses about techniques used for imaging of these radionuclides for better therapy and diagnosis of the root cause of the concerned disease by positron emission tomography (PET)/CT and single photon emission computed tomography (SPECT)/CT as well as the advantages and disadvantages associated with them. It also describes about applications of theranostics and nuclear imaging in cancer treatment and their future perspective.

Parathyroid Scintigraphy

The visualization of abnormal parathyroid glands is difficult due to their variations in number and localization. Noninvasive parathyroid imaging studies include 99mTc-sestamibi scintigraphy, ultrasonography, computed tomography scanning, magnetic resonance imaging, and positron emission tomography. There is a general consensus that the most sensitive and specific imaging modality, especially when it is combined with single-photon emission CT is the scintigraphy with 99mTc-sestamibi or 99mTc-tetrofosmin. 99mTc-sestamibi scintigraphy significantly increases the role of preoperative scintigraphy in patients with hyperparathyroidism and allows unilateral surgical approach with minimally invasive parathyroidectomy to be used. Generally, three protocols with the use of two radiopharmaceuticals, 99mTc-sestamibi or 99mTc-tetrofosmin, are most widely applied: single-phase dual-isotope subtraction, dual-phase single-isotope and combination of both. Each one of them has specific advantages and disadvantages. While single parathyroid adenomas are localized with greater precision, hyperfunctioning parathyroid hyperplastic cells represent a real challenge to the imaging modalities. Several factors can influence the radionuclide uptake in pathologically changed parathyroid cells, like the size, the level of their functional activity, the quantity of oxyphilic cells, mitochondria, P glycoprotein and other MDR gene products.

Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging - A Lot to Consider

Gallium-68 was applied for positron emission tomography (PET) imaging already in the early beginnings of PET imaging. Today, with the introduction of PSMA-targeting tracers (e.g. PSMA-11, PSMA-617, and PSMA-I&T), the number of clinical applications of 68Ga-radiopharmaceuticals for diagnostic imaging has grown considerably. This development was initiated and supported already in the mid-2000s by the commercial availability of 68Ge/68Ga generators designed for clinical usage. This progression was accompanied by the development of several purification methods to generator eluate as well as sophisticated 68Ga-radiopharmaceuticals. Due to the 68Ga-rush, the need for implementation of gallium-68 (depending on production route) and its certain tracers into the pharmacopeia increased. Based on the specifications given by the pharmacopeia, interest focused on the development of automated synthesis systems, 99mTc-analog kits with regard to patient as well as operator safety.