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

Another 18F-labeled PET radiopharmaceutical for in vivo detection of amyloid deposits is 18F-
Flutemetamol. This radiopharmaceutical is a structural analog of PiB offering much wider accessibility for
[29]
both clinical and research use due to its longer physical half-life . The first observation of myocardial
uptake of 18F-Flutemetamol in CA was published in 2014 and referred to a single case of AL compared with
2 healthy volunteers ; a pilot study performed in 2019 on nine patients with amyloidosis compared with 3
[30]
control subjects described a significantly greater myocardial accumulation of the radiopharmaceutical in
subjects with cardiac amyloidosis compared to controls . More recently, Möckelind et al. evaluated the
[32]
[31]
use of 18F-Flutemetamol in a group of 21 selected patients affected by a hereditary form of ATTR with
negative osteophilic tracer scintigraphy compared with 6 control subjects. Patients with ATTR showed high
myocardial radiopharmaceutical uptake, and the method was able to identify patients with high accuracy
[32]
(sensitivity, 88%; specificity, 100%). Möckelind et al. concluded that this method could be useful for the
evaluation of patients with clinical suspicion of ATTR and negative 99mTc-DPD scintigraphy.

The last radiopharmaceutical labeled with 18F for in vivo detection of amyloid deposits is 18F-
Florbetaben . This radiopharmaceutical has also been shown to have affinity for cardiac amyloid deposits,
[33]
[34]
and, in 2016, the first study in this area was published . In this pilot study, the authors compared a
heterogeneous group of patients with CA (5 AL and 5 ATTR) with a control group consisting of patients
with hypertensive heart disease; they concluded that this radiopharmaceutical may represent a promising
tool for the diagnosis of cardiac amyloidosis, without any evidence of its ability to differentiate between AL
and ATTR.

More recently, Kircher et al. evaluated the diagnostic performance of 18F-Florbetaben in a group of 14
[35]
patients with CA (5 ATTR, 8 AL, and 1 AA) and 8 patients with cardiomyopathy. In 4 patients, they were
also able to evaluate the PET/CT data during the follow-up. The results indicate that PET/CT with 18F-
Florbetaben can discriminate between CA and non-infiltrative cardiomyopathy and that the myocardial
retention index of the radiopharmaceutical is higher in AL than ATTR. Furthermore, the results derived
from the evaluation of the small group of patients with re-evaluation after therapy seem to suggest a
[35]
potential role of this radiopharmaceutical for the evaluation of the response to therapy .
All studies described thus far have taken into consideration data obtained in very early stages of the tissue
distribution of the radiopharmaceutical.

A recently published work evaluates the diagnostic performance of 18F-Florbetaben PET/CT in a group of
40 patients with CA (20 AL and 20 ATTR) compared with a control group of 20 patients with non-
[36]
infiltrative hypertrophic cardiomyopathy . The authors evaluated quantitative parameters derived from
dynamic acquisitions lasting 60 min and four static reconstructions lasting 10 min obtained, respectively, 5,
30, 50, and 110 min after the injection of the radiopharmaceutical. All quantitative parameters were
significantly greater in patients with AL than in those with ATTR and controls. Moreover, the washout rate
of the radiopharmaceutical between 5 and 60 min after injection was significantly higher in the ATTR group
and the controls compared to the AL group, suggesting a greater affinity of the radiopharmaceutical for the
amyloid substance derived from immunoglobulin light chains. The authors concluded that a late evaluation
of the myocardial uptake of this radiopharmaceutical obtained at least 30 min after injection allows
identifying the AL forms, differentiating them from ATTR and mimicking conditions.

OSTEOPHILIC RADIOPHARMACEUTICALS
Some radiopharmaceuticals originally developed to study bone metabolism and labeled with 99mTc have
been successfully used for the demonstration of amyloid cardiac involvement. These radiopharmaceuticals