**2. Application: why choosing a radiometal?**

What is the advantage of radiometals for an application in nuclear medicine? With carbon-11 and mostly fluor-18, two radionuclides for positron emission tomography (PET) are available, which can be used for radiolabeling without appreciably altering the biological properties of the compounds in addition to their favorable decay characteristics. However, the disadvantage of radiometals, the need for a chelator is also their advantage over fluor-18 and carbon-11.

Due to this, radiolabeling with radiometals is very easy, can be conducted in aqueous solution and with the right choice of chelator possible under mild conditions. That enables radiolabeling of temperature or organic solvent sensitive compounds (e.g. antibodies). Additionally, the choice of chelator provides the possibility of radiolabeling one compound with different radiometals. Thus,

#### **Figure 1.**

*Depiction of the theranostic concept: utilizing one compound for a variety of applications in patient-centered care radiolabeled with different radionuclide.*

**25**

[

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

widespread application (PET, single photon emission computed tomography (SPECT), magnet resonance tomography (MRT) and therapy) of the compound only by exchange of the radiometal with minimum changes in biological behavior is possible. This facilitates patient-centered care from diagnosis via molecular imaging, over treatment planning, prognosis and monitoring utilizing one com-

*PET-images (A; C) and SPECT-images (B) of a patient with metastatic castrate-resistant prostate cancer (mCRPC) undergoing therapy with [177Lu]Lu-PSMA-617 with pre- and posttherapeutic 68Ga-PET-imaging* 

**3. Current applications of 68Ga-radiopharmaceuticals**

the extension of the application scope.

Advantages in favor of gallium-68 compared with other appropriate radiometals are its favorable decay characteristics, its (commercial) availability and the possible combination with lutetium-177 as theranostic pair (**Figure 2**). Also gallium-68 possibly provides patient care in places where cyclotron-produced fluor-18 is not obtainable.

Currently gallium-68 is most widely used in the diagnosis of prostate cancer in the form of [68Ga]Ga-PSMA-11, respectively. [68Ga]Ga-PSMA-617 together with

The second, but longest known and best evaluated, 68Ga theranostic pair is used

for neuroendocrine tumors in combination with various somatostatin analogs. The three most widely used analogs of somatostatin with gallium-68 are [68Ga] Ga-DOTA-TOC, [68Ga]Ga-DOTA-TATE, [68Ga]Ga-DOTA-LAN or [68Ga]Ga-DOTA-NOC [15]. As a therapeutic counterpart, yttrium-90 and lutetium-177 are used. Besides these two main applications of gallium-68, a variety of studies work on

For imaging of insulinoma pancreatic islets, several versions of 68Ga-radiopharmaceuticals based on Exendin-4, a glucagon-like protein-1 receptor agonist, exist and it was demonstrated that [68Ga]Ga-DOTA-exendin-4 localizes insulinoma significantly better than 111In-radiolabelled radiopharmaceuticals [16]. Integrin αvβ3 and gastrin-releasing peptide receptor (GRPR) are usually overexpressed in human breast cancer, prostate cancer, breast cancer, colorectal cancer, pancreatic cancer, glioma, lung cancer, ovarian cancers, endometrial

177Lu]Lu-DOTA-PSMA-617 forms a theranostic couple, which is very well suited for the diagnosis or treatment of prostate cancer as the 68Ga/177Lu-radiolabelled tracers show a very similar biological behavior. Due to similarities in chemical behavior, identical (in case of PSMA-617) precursors can be radiolabelled using the

same or similar equipment, synthesis and quality control methods [14].

*DOI: http://dx.doi.org/10.5772/intechopen.90615*

*using the diagnostic counterpart [68Ga]Ga-PSMA-11.*

pound (**Figure 1**).

**Figure 2.**

*Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging - A Lot to Consider DOI: http://dx.doi.org/10.5772/intechopen.90615*

**Figure 2.**

*Medical Isotopes*

(gallium-68, 12 trials between 1991 and 2011; lutetium-177, 16 trials between 1996 and 2011) both have increasingly found application in clinical routine reflected in

Although, gallium-68 was already proposed for medical use by Gleason [10] its way to clinical application was not possible without the advancement of the primary generator design. Providing [68Ga]GaCl3 and containing only trace levels of the long-living mother radionuclide germanium-68 regarding 68Ga-activity, the commercially availability of generator simplified research and motivated developments with a view to a broad routine application. The launch of this new type of 68Ga-generator together with decades of research in chelation chemistry and drug discovery resulted in the design of 68Ga-radiopharmaceuticals of high affinity/selec-

The advantages of the generator availability and the easy one-step chelation chemistry ensured the relatively fast and broad application of the 68Ga-radiopharmaceuticals even in smaller institutions. However, exactly these advantages lead to problems in the supply today and require new developments in

What is the advantage of radiometals for an application in nuclear medicine? With carbon-11 and mostly fluor-18, two radionuclides for positron emission tomography (PET) are available, which can be used for radiolabeling without appreciably altering the biological properties of the compounds in addition to their favorable decay characteristics. However, the disadvantage of radiometals, the need

Due to this, radiolabeling with radiometals is very easy, can be conducted in aqueous solution and with the right choice of chelator possible under mild conditions. That enables radiolabeling of temperature or organic solvent sensitive compounds (e.g. antibodies). Additionally, the choice of chelator provides the possibility of radiolabeling one compound with different radiometals. Thus,

*Depiction of the theranostic concept: utilizing one compound for a variety of applications in patient-centered* 

the rapidly increasing amount of enrolled phase 1–3 studies.

tivity for their biological targets [11–13].

order to meet the growing demands.

**2. Application: why choosing a radiometal?**

for a chelator is also their advantage over fluor-18 and carbon-11.

**24**

**Figure 1.**

*care radiolabeled with different radionuclide.*

*PET-images (A; C) and SPECT-images (B) of a patient with metastatic castrate-resistant prostate cancer (mCRPC) undergoing therapy with [177Lu]Lu-PSMA-617 with pre- and posttherapeutic 68Ga-PET-imaging using the diagnostic counterpart [68Ga]Ga-PSMA-11.*

widespread application (PET, single photon emission computed tomography (SPECT), magnet resonance tomography (MRT) and therapy) of the compound only by exchange of the radiometal with minimum changes in biological behavior is possible. This facilitates patient-centered care from diagnosis via molecular imaging, over treatment planning, prognosis and monitoring utilizing one compound (**Figure 1**).

Advantages in favor of gallium-68 compared with other appropriate radiometals are its favorable decay characteristics, its (commercial) availability and the possible combination with lutetium-177 as theranostic pair (**Figure 2**). Also gallium-68 possibly provides patient care in places where cyclotron-produced fluor-18 is not obtainable.
