imaging and therapy [2, 3]. The advantageous photophysical properties of porphyrin derivatives have led to roles in many biomedical applications, particularly in
photodynamic therapy (PDT) and molecular imaging. The characteristic of some
tetrapyrroles to accumulate in tumors is used for these applications [4].
The history of porphyrins in PDT has been described in the literature [5–7]. In
1912, Meyer-Betz observed the photodynamic effect by injecting himself with
hematoporphyrin and subsequently exposing small regions of skin to light. In 1924,
Policard observed natural porphyrin fluorescence in experimental tissue. In 1961,
the tumor-localizing properties of a hematoporphyrin derivative (HPD) and its
detection by fluorescence were discovered by Lipson and photosensitization of
porphyrins for eradication of experimental tumors in animals was reported later.
The preparation of HPD as reported by Lipson was the basis for the subsequent use
of Photofrin
® for PDT.
Phthalocyanines (Pcs) are structurally related to porphyrins but do not occur
naturally. The term was coined in 1933, by Sir Reginald Linstead, who also
determined the structure [8]. The structure of Pc is similar to that of porphyrins and
Fig. 3.1b shows the structure for simple metal-Pcs [9]. Pcs have found numerous
applications from colorants to catalysts. Pc derivatives of different charge and
lipophilicity can be prepared by the addition of the appropriate substituents on the
benzene rings of the macrocycle [10]. One application of note for Pcs is the use of
tetrasulfonated phthalocyanine (PcS 4 ) which has been used clinically as Photosens
[11]. Recently, Pcs have been explored in numerous theranostic application [12].
Porphyrins and Pcs have been used extensively for photosensitizers and radiolabeling [13]. Cu-phthalocyanine was described as a
64 Cu chelator that accumulated
in rodent brain tumors as early as 1951 [14]. These molecules are useful for use as
radiochelators, for image-guided PDT, and for building more complex structures
with imaging capabilities for disease detection.
3.1.2 Radionuclides for Labeling Porphyrins
and Phthalocyanines
The radioactive decomposition of radionuclides into subatomic particles or protons
allows for sensitive imaging and tracking. With nuclear medicine technology such
as positron emission tomography (PET) and single photon emission tomography
(SPECT), compounds labeled with c or positron emitting radionuclides are viable
for whole body in vivo imaging [5] (Fig. 3.1c). Radiolabeling can enable quantitative whole body imaging of compound distribution. Various techniques for
radiolabeling are illustrated in Fig. 3.2a the radionuclide is attached to a nanoparticle surface by an exogenous chelator; (B) the radionuclide is entrapped in an
enclosed compartment; or (C) nanoparticles are manufactured from
pre-radiolabeled building blocks [15]. The specific localization and sensitizing
ability of porphyrins for tumor imaging and biodistribution studies are generally
3 Porphyrin and Phthalocyanine Radiolabeling
51
photodynamic therapy (PDT) and molecular imaging. The characteristic of some
tetrapyrroles to accumulate in tumors is used for these applications [4].
The history of porphyrins in PDT has been described in the literature [5–7]. In
1912, Meyer-Betz observed the photodynamic effect by injecting himself with
hematoporphyrin and subsequently exposing small regions of skin to light. In 1924,
Policard observed natural porphyrin fluorescence in experimental tissue. In 1961,
the tumor-localizing properties of a hematoporphyrin derivative (HPD) and its
detection by fluorescence were discovered by Lipson and photosensitization of
porphyrins for eradication of experimental tumors in animals was reported later.
The preparation of HPD as reported by Lipson was the basis for the subsequent use
of Photofrin
® for PDT.
Phthalocyanines (Pcs) are structurally related to porphyrins but do not occur
naturally. The term was coined in 1933, by Sir Reginald Linstead, who also
determined the structure [8]. The structure of Pc is similar to that of porphyrins and
Fig. 3.1b shows the structure for simple metal-Pcs [9]. Pcs have found numerous
applications from colorants to catalysts. Pc derivatives of different charge and
lipophilicity can be prepared by the addition of the appropriate substituents on the
benzene rings of the macrocycle [10]. One application of note for Pcs is the use of
tetrasulfonated phthalocyanine (PcS 4 ) which has been used clinically as Photosens
[11]. Recently, Pcs have been explored in numerous theranostic application [12].
Porphyrins and Pcs have been used extensively for photosensitizers and radiolabeling [13]. Cu-phthalocyanine was described as a
64 Cu chelator that accumulated
in rodent brain tumors as early as 1951 [14]. These molecules are useful for use as
radiochelators, for image-guided PDT, and for building more complex structures
with imaging capabilities for disease detection.
3.1.2 Radionuclides for Labeling Porphyrins
and Phthalocyanines
The radioactive decomposition of radionuclides into subatomic particles or protons
allows for sensitive imaging and tracking. With nuclear medicine technology such
as positron emission tomography (PET) and single photon emission tomography
(SPECT), compounds labeled with c or positron emitting radionuclides are viable
for whole body in vivo imaging [5] (Fig. 3.1c). Radiolabeling can enable quantitative whole body imaging of compound distribution. Various techniques for
radiolabeling are illustrated in Fig. 3.2a the radionuclide is attached to a nanoparticle surface by an exogenous chelator; (B) the radionuclide is entrapped in an
enclosed compartment; or (C) nanoparticles are manufactured from
pre-radiolabeled building blocks [15]. The specific localization and sensitizing
ability of porphyrins for tumor imaging and biodistribution studies are generally
3 Porphyrin and Phthalocyanine Radiolabeling
51