Radiolabelled peptides and hormones presented in the class of inorganic and it is according to the chemistry

2. Radiolabelled peptides and
hormones
Presented by:
Sumra Idrees (574)
Presented to:
Sir Tanveer bukhari
GCUF

3. Peptides have an important role in fundamental body
functions as cell signaling and homeostasis
Recently these are focused of much interest as are being
used in diagnostic radiopharmaceuticals
Peptides show a logical radiopharmaceutical
development
Introduction

4. Introduction conti……
• For tumor imaging these receptors are
considered prospective molecular
targets
• as well as targeted radiotherapy by the
help of radiolabeled peptides
• In neuroendocrine tumors (NETs),
somatostatin (SST) is the finest exemplar
receptor overexpression which are
presently being embattled effectively by
SST analogs, n-DTPA-octreotide

5. Introduction conti…….
• The high level expression of SST receptors on a
variety of cancers has given the molecular root
for the achievement of In-OctreoScan
• like a tumor targeting peptide and it opens fresh
avenues for the growth of other tumor-specific
peptides through potential utilize in nuclear
oncology

6. Tremendously high affinities (nano- or subnanomolar
range)
for cell-surface receptors are shown by naturally
happening peptides
Introduction conti……

7. Types of peptides
1. Gastrin-releasing
peptides and
bombesin
2. Vasoactive
intestinal peptide
3. Glucagon-like
peptide
4.Natural Biologically
active Peptides

8. Gastrin-releasing peptides and
bombesin
• Gastrin-releasing peptide (GRP) and bombesin can fasten to G-
coupled GRP receptors which are ubiquitous on cells of numerous
frail somebody types
• such as endocrine, tit and pancreatic house and small-cell lung
carcinoma
• Bombesin is a dwarfish neuropeptide of 14 radical acids which has
been unaccompanied from frogs,
• whereas GRP, the earthborn writing of this bombesin, consists of
27 alkane acids

9. Both peptides pretense have same natural behavior in
humans, which can be explained by only infinitesimal
structural differences between the two molecules
The protection computer of bombesin consists of figure
amino resolvent residues
And in the literature peptides which incorporate this
octapeptide are ordinarily termed bombesin
Gastrin-releasing peptides and
bombesin

10. Vasoactive intestinal peptide
• Vasoactive enteral peptide (VIP) and pituitary adenylate
cyclase-activating peptide (PACAP), which are both Secretin
like peptides,
• Are neuropeptides which determine a catholic spectrum of life
activities
• including vasodilatation,
• stimulation of secretion of different hormones,
• immunomodulation and advancement of cadre proliferation

11. Vasoactive intestinal peptide
• VPAC1 is verbalized in the mentality and
most epithelial tissues
• VPAC2 is only inform in suave tough
• The VPAC1 receptor is the only
VIP/PACAP receptor saved on neoplasm
cells of neuroendocrine origin and
neuroblastomas
• But in medullary endocrine cancers,
VIP/PACAP receptors are gone

12. Vasoactive intestinal peptide
• Latterly a many lasting
64Cu-labelled VIP
analog has been
formed for
neuroendocrine
• And manlike face
tumours, that shows a
higher tumour uptake
than the 99mTc-
labelled VIP linear

13. Glucagon-like peptide 1 (GLP-1) receptors belong to the G coupled
accelerator organ set
Physical organ reflection in humans is controlled to the endocrine
organ, duodenum and pancreas
The operate of these GLP-1 receptors is not yet completely
comprehended
But receptor information seems to lead in humour of insulin
calcitonin and augmented proliferation of tumour cells with inhibited
apoptosis
Glucagon-like peptide

14. Recent studies tally
shown the clinical
voltage of the GLP-1
receptor
Antimicrobial
peptides
which are mainly
produced by
phagocytes and
endothelial cells
Are heavy factor of
the innate immune
group, providing
security against
microorganism
attacks
Glucagon-like peptide

15. Glucagon-like peptide
• Manlike neutrophile peptide 1-3 (HNP 1-3) is a
defending that induces the creation of
lymphokines
• And promotes T-cell and antigen-specific body
production
• This peptide is apace improved from the
circulation via the kidneys and vesica with low
reflex
• But growth in the gallbladder and the intestine
makes it unfavorable ammunition for the espial of
abdominal infectionsion in the liver

16. Natural Biologically active Peptides
• Peptides are obligatory elements in solon
basic life processes than any added
category of corpuscle
• For ideal, peptides role as hormones,
neurotransmitters, neurornodulators,
ontogenesis and ontogeny forbiddance
factors and cytokines

17. Natural Biologically active Peptides
• The molecular weights of biologically active peptides are
extremely different
• Ranging from 3 to 5 residues in TRH, enkephalins and bacterial
chemoattractant peptides to over 200 residues in ontogenesis
hormone
• For instance in PTH and ACTH, biological reflection is given by
the N-terminal sequence

18. Two major categories of methods for synthesizing peptides:
1.solution-phase in addition to solid-phase peptid
2.Merrifield’s SPPS Method
Peptide synthesis

19. solution-phase in addition to solid-phase peptid
• The ‘‘traditional’’ solution-phase
synthesis procedure has some degree of
applications in modern fast emergent
peptide fielde synthesis
• This method frequently requires complex
and lengthy purification process that’s
why it is difficult, expertise exhaustive
• as compared to this method, Merrifield’s
SPPS is at this time the favored process
for peptide synthesis

20. It requires fewer purifications
and minimal optimization of
the reaction condition that’s
why SPPS is a speedy and
trouble-free approach
The significant development in
the field of peptide formation
over the preceding numerous
years has brought innovation
of a large diversity of bioactive
peptides
Merrifield’s SPPS Method

21. FIG: scheme of peptide labeling

22. How radiolabeleled peptides are
used for diagonastic propose
• The scrutiny specialism of atomic
medication focuses on the
application of radiolabelled
tracers for scintigraphic imaging
• or radionuclide therapy of disease
• The modern phylogeny of
knowledge in molecular
accumulation has resulted in new
targets to find weak somebody
specifically

23. How radiolabeleled peptides are used
for diagonastic propose
• New developments in (broadcasting) immunology someone
landscaped molecular transfer of radionuclides to disease-target
sites
• Consequently this has resulted in the breeding of novel tracers
• Specialised developments in scintigraphic instruments and
recollection software feature restored picturing modalities
• allowing small-animal scintigraphic

24. How radiolabeleled peptides are used
for diagonastic propose
• A auspicious possibleness for atomic applications in oncology lies in
the utilization of radiolabelled peptides that point receptors for
picturing and therapy
• Linked to apropos therapeutic radionuclides these peptides can also
be utilized as radiotherapeutics in peptide organ radionuclide
therapy (PRRT)

25. Fig: peptides as
diagnostic tools

26. Radio labeling of peptides
• Attaching an immense chelating moiety or a prosthetic group
to small size peptides
• and adding a radiolabel can manipulate the fastening affinity
and pharmacokinetic properties of a peptide
• That’s why, for flourishing radio labeling with the preferred
radionuclide a watchful variety of a chelating group and site-
specific radio labeling is essential

27. An extensive range of prosthetic groups and
chelating agents have been made in current
years
for the suitable radio labeling of peptides
with a variety of radionuclides
Several radionuclides, either therapeutic
(177Lu, 90Y)
or diagnostic (18F, 64Cu, 111In, 123I, 68Ga,
99mTc), have been used for radio labeling
Radio labeling of peptides

28. Peptides are made up of the similar basic structural blocks as
proteins, therefore techniques which have been developed for
radio labeling
as peptides have smaller number of amino acid residues as
compared to proteins therefore there are fewer sites vacant for
labeling
RADIOLABELING TECHNIQUES

29. RADIOLABELING TECHNIQUES
• Definite activity becomes a serious element in the synthesis of
radiolabeled peptides
• due to the elevated influence of numerous peptides and the
small tissue concentrations of their target receptors
• Varieties of methods for labeling proteins with radioisotopes of
carbon, fluorine, iodine, technetium, gallium and iridium have
been developed for the time of more than ten years

30. It is the most
broadly utilized
technique for
radio labeling of
peptides
For in-vitro
applications of
radioabeled
peptides initially
it was
developed,
such as in RIA
assays, radio
iodination have
great
applications for
imaging
purposes
For all this to
happen there is
the need of
isotopes like
Iodine-123 and
Iodine-124, as
well as Iodine-131
Iodination

31. Iodination
• For direct iodination Reagents are available including the
commonly used agents, like iodine monochloride N-
bromosuccinimide, Iodogenand and Chlorarnine T
• we can achieve Quantitative labeling with most peptides by
changing the conditions of reaction
• and the elimination of unnecessary radioactive by-products

32. Iodination
• chromatographic techniques like ion
exchange and reverse-phase are used for
purification of the radiolabeled peptide
• One probable disadvantage of radio
labeling using iodine for peptides is the
examining in vivo of speedy
dehalogenation

33. N-succinimidyl- 4 Iodobenzoate N-succinimidyl -3-Iodobenzoate
N-succinimidyl -5 -Iodo-3-pyridine
carboxylates
In common, these reagents
express larger in vivo strength as
compared to directly labeled
polypeptides and also trialkyl
stannyl precursors are building
blocks of these reagents
Radio labeling reagents

34. Radio labelling techniques
• For lowering in vivo dehalogenation the structural necessities
has been seen it includes (a) the linkage nature of polypeptide
(b) length of alkyl chain and (c) the substituent’s of ring
• for scintigraphic imaging of peptides Iodine-131
• High radiation, high cost, the limited availability and the
reduced imaging behavior of Iodine-123 are now linked with
Iodine 131 Iodine-123 have been used

35. Technetium-99m
• Because of its low cost
• comprehensive ease of use,
• outstanding imaging characters, and encouraging
dosimetry technetium-99 is a perfect radionuclide
for peptide labeling
• More ever, Tc-99m can too be obtained at sky-
scraping definite action
• Tc-99m labeling chemistry is enhanced definite
and additional expected by using the bifunctional
chelate or indirect method

36. Group III metal Iridium-l11 has a
chemistry and half-life which
makes it perfect for radio
labeling integral immunoglobulin
The PE isotope, Gallium-68 was
used for radio labeling chemo
tactic peptides
and a somatostatin analog using
DTPA and desferrioxamine as
bifunctional chelates,
correspondingly
Indium-111 and Gallium-68

37. Development of a peptide-based Radiopharmaceutical
• To build up a new radiopeptide, a natural or
synthetic peptide should be radiolabeled
competently with high precise radioactivity
• and be constant under physiological situation
• The new peptide should be able to exhibit an
elevated tumor uptake and maintenance in vivo
with low environment radioactivity

38. Continue……….
• A pure negatron emitter
• Medium- or high-energy particle
• Moderately long effective half-life
• High target-nontarget ratio
• Readily available and inexpensive
• Minimal radiation dose to personnel
• - Provides high linear energy transfer
-Decreases radiation dose to adjacent normal tissues
• - Energies greater than 1 maximum beta-energy (meV)
• - Typically in days
- Easy to control dosimetry
• - Decreases exposure of normal tissues
- Provides selective delivery of radiation
• - Increases use at many institutions
• - Easy to control with negatron emitters

39. Tumor imaging peptide
radiopharmaceuticals
To make radiolabeled peptide clinically functional for tumor
imaging it should have following properties:
(i) high precise uptake and preservation in tumors
(ii) tall in vivo stability
(iii) effortlessness of preparation
(iv) elevated affinity for the target receptor

40. The victorious utilization of
radiolabelled peptides like radio
diagnostics has been translated into
the expansion of peptide receptor
radionuclide therapy
The dictatorial peptide has also been
radiolabelled for finding targets in
vivo as their receptors are repeatedly
over articulated in a diversity of nasty
tumours
Applications of polypeptides as
imaging probes

41. The most excellent outcome so far have been achieved in comparatively
radiosensitive lymphomas
Clinical trials correspondingly can be made effective, which can decrease the number
of effected people treated with unsuitable doses
Applications of polypeptides as
imaging probes

42. Positron emission tomography as
the imaging technique
• Positron emission tomography is
an in vivo tomographic imaging
method
• Its base is actually the finding of
anti-parallel 511 keV photons
emitted throughout the total
destruction of positrons with
electrons
• The positrons approach from the
decompose of positron-emitting
nuclides

43. Fig
PET

44. Advantages and limitations of
peptide-based Radiopharmaceuticals
• Advantages
• Minute peptides are important tools
for peptide receptor radiotherapy and
tumor diagnosis
• Easy to synthesize and manipulated
molecularly to make their affinity sure
for a meticulous receptor and to
exhibit a more specific biodistribution
outline

45. Advantages
• capability to go
through into tumors
sooner than
monoclonal
antibodies.
• capability to bear the
cruel conditions like
pH, temperature, etc.
of chemical alteration
or radio labeling

46. Disadvantages
• The enzymatic annihilation can be repressed by molecular
changes:
• the replacement of D-amino acids for logically occurring L-
amino acids the amalgamation of amino alcohols, the insertion
of unnatural amino acid or side chains or amidation
• Peptides may be capable to persuade pharmacologic special
effects even in low amounts

47. Disadvantages
• failure of binding likeness upon combination with a chelator .
• Problem can be decreased by site-directed radio labeling that
can be achieved by inserting a spacer group between the
binding series and the chelating moiety
• No doubt radiolabelled peptides have their on importance but
there are drawbacks too as nothing are unique in this universe.

48. Conclusion
• Radiolabelled peptides know tremendous possibleness for
clinical good
• In oncology many (new) peptides are existence mature and
evaluated for both characteristic and therapeutic use
• An intriguing usage is the usage of sharp peptides, which
strength is real reusable in precise growth targeting