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Page 4 of 11 Genovesi et al. Vessel Plus 2021;5:50 https://dx.doi.org/10.20517/2574-1209.2021.67

results, 123I-MIBG scintigraphy is rarely used in the diagnostic work-up of CA.

RADIOPHARMACEUTICALS FOR AMYLOID SUBSTANCE
All amyloid deposits contain a non-fibrillar glycoprotein called the “P component of the amyloid”. The P
component of serum amyloid labeled with 123I (123I-SAP) is a scintigraphic radiopharmaceutical which
binds to all types of amyloidogenic fibrils and can be used to identify the presence and distribution of
[20]
amyloid deposits [19,20] . Hazenberg et al. evaluated the diagnostic accuracy of this method: the sensitivity
was 90%, 90%, and 48% in subjects with biopsy evidence of AA, AL, and ATTR amyloidosis, respectively,
with a specificity of 93%. Nevertheless, cardiac involvement was not identified in any patient. For this
reason, in addition to the poor quality of the images obtained, the cost of the radiopharmaceutical, and its
limited availability in many countries, 123I-SAP is not widely used for the assessment of CA.

A radiopharmaceutical that is more available, more easily labeled, and with a more favorable energy peak
and has been used in the past is 99mTc-aprotinin. Aprotinin is a protease inhibitor which accumulates in
the tissues affected by amyloid substance deposition and can allow visualizing CA . Unfortunately, even
[21]
this radiopharmaceutical has not been shown to have a high binding specificity for amyloid deposits in the
heart; in fact, in patients with biopsy-proven CA, the identification rate of cardiac involvement was between
36% and 44% [21,22] .

Positron-emitting radiopharmaceuticals with binding affinity for amyloid all originate as in vivo tracers of
cerebral beta-amyloid deposits for diagnostic confirmation of Alzheimer’s disease; some of these
radiopharmaceuticals have subsequently also shown binding affinity for myocardial amyloid, both in the
context of a systemic amyloidosis with cardiac involvement and in the case of isolated CA.

The first PET radiopharmaceutical for the study of amyloid deposits was patented in the early 2000s under
the name of Pittsburgh Compound B (PiB); this radiopharmaceutical is a derivative of Thioflavine T (a dye
[23]
for histological preparations that binds specifically to amyloid deposits) and is labeled with 11C . The first
prospective study performed on a small group of subjects to evaluate the usefulness of PiB in the diagnosis
of CA was published in 2013 . In this study, the authors described a significant early myocardial uptake of
[24]
the radiopharmaceutical (approximately 15-25 min after injection) in all 10 patients with amyloidosis and in
no control subjects (n = 5), suggesting a possible use of this method for the diagnosis of cardiac involvement
in the case of systemic amyloidosis. Unfortunately, the short decay time of 11C allows the use of this
radiopharmaceutical only in centers equipped with a cyclotron.

Since 2009, some PET radiopharmaceuticals labeled with 18F with high affinity for beta-amyloid have been
developed. The first of these new radiopharmaceuticals is 18F-Florbetapir, a structural analog of stilbenic
dyes used in histology ; as for PiB, this radiopharmaceutical has also been developed for the in vivo
[25]
diagnosis of AD and studies performed in humans have demonstrated its usefulness in this sense, making it
the first available 18F-labeled PET tracer for brain amyloid [26,27] . The first pilot study demonstrating the
[28]
affinity of 18F-Florbetapir for myocardial amyloid deposits was published in 2014 ; the authors evaluated
14 subjects including 9 patients with cardiac amyloidosis and 5 control patients with non-infiltrative
hypertrophic cardiomyopathy. Patients with cardiac amyloidosis showed significantly greater myocardial
uptake of the radiopharmaceutical than controls both in SUV values and in target-to-background ratios;
image analysis did not allow a differential diagnosis between AL and ATTR, but the higher myocardial
retention index in the group of patients with AL suggested a higher avidity of AL than ATTR for
Florbetapir.